Support Care Cancer (1995) 3:331-383 Springer-Vertag 1995

Chair: 7th International Symposium M. Dicato, M.D. Supportive Care in Cancer, Luxembourg, 20-23 September 1995

20 September 1995 The Neutropenic Cancer Patient Chair: R. Feld, M.D.

21 September 1995 Nausea and Vomiting Chair: M.S. Aapro, M.D., and M. Tonato, M.D.

Cytokines Chair." W.P. Peters, M.D., Ph.D.

22 September 1995 Pain Chair: W. O'Neill, M.D.

Metabolism and Nutrition in the Cancer Patient Chair: H.J. Senn, M.D.

Psychosocial Support Chair: A. Glaus, R.N., M.Sc.

23 September 1995 Specialized Care of the Critically III Cancer Patient Chair: J.P. Sculler, M.D.

Toxicity-reducing Agents Chair: F. Ries, M.D.

Oral presentations are marked with an * 332

1" NATURE AND OUTCOME OF FEBRILE presence of shock (P < 0.0001), resistance of the causative pathogen EPISODES IN PATIENTS WITH HEPATO- to the initial antibiotics (P < 0.0001) and bacteremia caused by either BILIARY AND PANCREATIC CANCER Pseudomonas (P = 0.03) or Clostridium spp. (P = 0.006). *Kenneth Rolston, MD., Saul Rodriguez, M.D., Granulocyte count recovery predicted superior survival rates (P < Edward Rubenstein, M.D. 0.0001), a finding which was more pronounced among pts with Department of Medical Specialties complex bacteremia (67% vs 87%, P = 0.02) than among those with The University of Texas M.D. Anderson Cancer Center simple bacteremias (92% vs 98%, P = 0.0004). Although initial Houston, Texas, U.S.A. monotherapy ofgm negative bacteremias and delay ofvancomycin in Febrile neutropenic patients (FNP) are routinely hospitalized for gm positive bacteremias resulted in poorer response to the initial administration of intravenous antibiotics. This strategy is derived from regimen, mortality was not significantly affected. data generated primarily from patients with hematologic malignancies Conclusions: Prognosis ofbacteremia in neutropenic cancer pts is (HM); but is often applied to other FNP. We reviewed 50 febrile significantly affected by the presence of complex infection, thus, it episodes in patients with hepatobiliary and pancreatic cancer to should be considered in therapy modifications and study analyses. elucidate the nature and outcome of these episodes and determine whether different strategies need to be developed for these patients. Results: Our results indicate that a higher proportion of these patients 3* Results of a sequential antimicroblal Therapy In patients with severe neutropenla and fever have documented infections (60%) and a lower proportion (24%) have Nowrousian MR, Werk S, Klaassen U, Kasper C., FUO than patients with I-IM. This is probably due to the fact that Fossa A, and Seeber S. most of these patients do not receive prophylactic antibiotics, in Department of Internal Medicine (Cancer Research),~ contrast to patients with HM. Tumor fever and drug fever are more University of Essen, FRG common in these patients than in patients with HM. Also, the majority tn a prospective study, we eva{uated the efficacy of a of infections are intestinal in origin, often polymicrobial, with sequential antimicrobial therapy in 97 patients (pts) with severe neutropenia Enterococcus and E. coli being predominant isolates, instead of and fever. 96% of the pts had haematological malignancies (46% acute cutaneous organisms such as S. epidermidis which predominate in myeloblastic leukaemia, 10% acute lymphoblastic leukaemia, 37% malignant lymphoma, 1% chronic myelocytic leukaemia in blast crisis, 2% patients with HM. Neutropenia (< 500 pmn/mm3) was present in only acute myelofibrosis) and 4% solid tumours. The median age of the pts was 10% - while local obstruction was a much more common predisposing 44 years with a range of 17-79 years. All pts had a peripheral blood factor, often leading to the development of cholangitis - a rare infection neutrophil count less than 500/gl and fever (>385~ at the beginning of in patients with HM. 32% of our patients were successfully managed antimicrebial therapy. In 60% of pts, the neutrophil count was less than 100/gl, and in 40% between 100-499/p.I. The median number of neutmphils without hospitalization and 94% survived their febrile episode. was 200/~1 during the first 10 days of treatment. Summary and Conclusion: There arg substantial differences among subsets of cancer patients regarding the nature and outcome of febrile Therapy strategy consisted of 1 to 3 phases according to the response of fever. Treatment started with a combination of piperacillin (3x4 g/d) and episodes. Since these differences often depend upon the nature of the netilmicin (lx400 mg/d)(phase I). If fever persisted during the first 72 hours, underlying malignancy, our data indicate the need for developing teicoplanin (lx400 mg/d) was added to this drug combination. If no response disease-site specific guidelines for the management of febrile episodes appeared during a further period of 72 hours, therapy was switched to in such patients. amphotericin B (0,5-1,2 mg/kg/d) and ceftazidim (3x2 g/d)(phase III). 18% of lots had fever of unknown origin (FUO), 43% bacteraemia, 25% pneumonia, and 14% soft tissue infection. FUO and Bacteraemia appeared more frequently in phase I and clinically documented infections particularIy OUTCOMES OF BACTEREMIA IN pneumonia in phase II or III of therapy. The response rate was 100% in pts 2* with FUO, 94% in 10ts with mucositis or other soft tissue infections, 93% in NEUTROPENIC CANCER PATIENTS: pts with bacteraemia, and 77% in those with pneumonia. A microbiologically INFLUENCE OF MAJOR ORGAN OR TISSUE documented infection was present in 72% of cases. In 69% of these INFECTION. *Linda S. Elting, Dr.P.H. and Gerald infections, Gram-positive bacteria, in 27% Gram-negative bacteria, and in P. Bodey, M.D. The University of Texas M. D. 4% fungi (candida) were, the causative organisms. 96% of the Anderson Cancer Center, Houston, Texas, U.S.A. micobiologieally documented infections responded to therapy. The response The epidemiology and outcomes of bacteremia rate was 100% in infections with Gram-positive bacteria, 89% in infections with Gram-negative bacteria, and 67% in those with fungi. Altogether 92% of among neutropenic cancer pts suggest that the 97 pts treated were cured. 67% of the 97 pts who entered phase I, 52% complex infection (major organ infection; soft tissue infection with of the 31 pts who entered phase II, and 62% of the 13 pts who entered phase necrosis or > 5 cm.) is an important predictor of response to therapy Ill of therapy were healed. 3% (3/97) of pts were suffered from persisting infection, and 5% (5/97) died. Death was due to infection in 1 patient, and and survival. Thus, we examined the prognostic significance of due to a progress of underlying disease in 4 patients. Median duration of complex infection and the effectiveness of treatment regimens in 909 therapy was 10 days. On the base of these results, the sequential episodes of bacteremia in neutropenic cancer pts. antimierobial therapy used appears to be highly effective in patients with Patients & Methods: A cohort ofbacteremic pts was selected from severe neutropenia and infection. The results in patients with pneumonia, 10 consecutive, randomized clinical trials of antibiotic therapy of however, demand further improvements. febrile neutropenia. Logistic regression was used to identify factors influencing 1) response to initial therapy, 2) ultimate outcome of ,4 ~ CORRELATION BETWEEN ANTIBIOTIC infection and 3) duration of survival. REGIMEN AND DURATION OF FEVER IN Results: 45% ofbacteremias were caused by gm positive organisms, GRAM NEGATIVE BACTEREMIAS (GNB) 43% by gm negatives and 12% were polymicrobial. 15% were *Linda S. Elting, Dr.P.H., Edward B Rubenstein complicated by complex infections, predominantly pneumonia or soft M.D., Kenneth Rolston, M.D. and Gerald P. tissue infection. The presence of complex infection significantly Bodey, M.D. The University of Texas M. D. decreased response to initial therapy (38% vs 75%, P < 0.0001), Anderson Cancer Center, Houston, Texas, U.S.A. ultimate outcome of infection (73 % vs 94%, P < 0.0001), and survival Numerous authors have noted that when broad spectrum, multidrug (P < 0.0001). Other factors associated with poorer outcomes were the coverage is provided empirically at the onset of febrile neutropenia, no 333

single regimen produces significantly higher survival rates among ~* WEEKLY ORAL FLUCONAZOLE (F) cancer pt s with GNB. Furthermore, the initial use of a 2-drug regimen 150 MG PROPHYLAXIS OF ORO- does not result in improved survival when compared with a 1-drug PHARYNGEAL CANDIDIASIS (OC) FOR regimen. We hypothesized that these regimens might differ with PATIENTS UNDERGOING ALLO-BMT: respect to the duration of fever and therapy and, thus, report the resuIts A PILOT STUDY of an analys~s of these factors in 380 neutropenic cancer pts with GNB *A. Puodziunas B.Sc.Phm,, G. Dranitsaris who had be6fi treated on 10 conse.c~tive clinical trials. M.Sc.Phm., H.Atkins M.D., A.McGeer Results: The mean duration of therapy was significantly shorter anmng pts who received 2-drug regimens initially (7 days) compared M.D., Departments of Pharmacy, i with those who received only 1 drug initially (9 days, P = 0.03). Microbiology and Medical Oncology. However, pts receiving single agent therapy with imipenem, aztreonam Princess Margaret Hospital, Toronto, or cefoperazone/sulbactam responded more rapidly than those Canada receiving other single agents or 2-drug regimens as illustrated below. OC can be a contributing cause of mucositis ,a common Regimen (Number of Pts.) 48 Hrs 72 Hrs % Su~,ival complication of allo-BMT. Allo-BMT patients are at risk of (% afebrile) .(%.afebrile) OC. Currently our patients receive oral nystatin solution 2 [3 - lactam (66) 3 76 93 500,000 units, swish and swallow, QID. Patients find this Amino + [3 - lactam (79) 1 73 95 difficult to take, unpalatable, and contributing to their nausea, Imipenem (29) 27 79 89 Ceftazidime (42) 0 71 88 resulting in poor compliance. Aztreonam (21) 14 73 92 It has been reported weekly oral F 150 mg is effective and Cefoperazone/sulbactam (43) 12 51 100 ,fell tolerated as prophylaxis for OC in moderately to severely Piperacillin (2t) 0 43 89 immunocompromised HIV patients, ls oral weekly F a useful Ticarcillin/clavulanate (16) 0 41 82 alternative fbr allo-BMT patients'? From an institutional Conclusions: Although 1 and 2-drug initial regimens resulted in perspective, antifungal prophylaxis should also be inexpensive similar survival, the duration of fever and therapy appear to be shorter and cost-effective. with some regimens, particularly those containing either 2 drugs or The study questions were: Is the incidence of local candidiasis imipenem. These findings have important implications for strategies using weekly oral F 150 mg equivalent to using oral nystatin employing early discharge of neutropenic cancer pts with febrile Is there increased patient compliance and/or preference with episodes; the cost-effectiveness of these regimens is being tested. weekly oral F 150 mg ? Frequency of positive candida isolates from throat swabs "k PULMONARY ASPERGILLOSIS IN ONCOHAEMA- was similar during l month before and 2 months after the TOLOGIC PATIENTS. RISK AND OUTCOME. introduction of weekly oral F 150 mg. 989/0 of patients did not *Fausto Rossini, M.D., E. M. Pogliani, M.D., S. Bolts M.D., Tien Tu Van, M.D., G. Cornco, M.D. attribute any S/E to the use of F. Hematology Unit. University of Milan. New Hospital. Conclusion: Weekly oral F 150 mg is a useful alternative for Monza, Italy prophylaxis of OC in the group of alto-BMT patients studied. Purpose of the study: Invasive pulmonary aspergillosis (PA) is a severe Calculated treatment costs for this study found F regimen to be complication in patients affected by hematologic neoplasias. We have comparable to nystatin and cost-effective. examined our patients affected by PA, trying to identify clinical or labo- ratory parameters associated with PA versus pneumonias of different etiology and to identify prognostic factors among patients affected by PA. Patients and methods: from April 89 to April 94 220 cases of pneumonia 7* TR I METHO P R I M/S UL FAMgI?I-IOXAZOLE ( TMS ) were diagnosed at our Unit in patients affected by hematological neopla- VERSUS TMS PLUS NORFLOXACIN(NFLX) sias. In 50/220 a diagnosis of mycotic pneumonia was made: 15 cases FOR PREVENTION OF NI~3TROPEN IG were microbiologically documented (10/15 autoptically); in 35 cases PA FEVER IN LUNG CANCER PATIENTS WITH was considered probable according to the score developed by Gerson (1). CHEMOTHERAPY- I NIXICED LEDKOPENIA. *Hideo Kuni toh, M.D., Akira Results and Conclusions: the score by Gerson (1) was shown to be able to Nagatomo, M.D., Hiroaki Okamoto, accurately diagnose PA in our group of patients: it was significant in M.D., Koshiro Watanabe, M.D. 14/15 microbiologically documented pneumonias. Dept. of Respiratory Medicine, Yokohama Besides three parameters included in the score (pleuritic chest pain, rales ,' lcMun ic i pa I Gitizen's Hosp., Yokohama, Japan. without volume overload, granulocytopenic days), the following parame- ters were significantly more frequently associated with mycotic pneu- TMS is widely used for prevention of monia: lower age (45 years vs. 53 - p=O.0003), male sex (78% vs. 60% - neutropenia-associated infection with cancer p=0.013), an absolute neutrophil count (ANC) lower than 500/ul at the chemotherapy. Increase of resistant bacteria diagnosis (76% vs. 38% - p<0.00001) and after seven days (68% vs. 34% necessitates more effect iv~e prophylaxic - p<0.00001); steroid therapy (56% vs. 41% - p=0.038) at the diagnosis. regimens. NFLX, a f luoroquinolone, has wide 23/50 (46%) patients with PA vs. 103/170 (61%) patients with pneu- antibacterial spectrum with good tolerance. monia of different etiology had a positive outcome (p=0.047). 24/50 pa- We conducted a randomized trial of TMS alone tients with PA died fo~"infection and 3 died for non infectious cause. versus TMS plus NFLX in lung cancer patients The most important determinant for the outcome of PA was the rise of with ehemotherapy-induced~ leukopenia, to ANC: at the day of first negative chest radiogram, only I patient had evaluate the efficacy of the combined persistent neutropenia (ANC < 500/ul); also patients receiving steroid regimen. A total of 133 episodes of grade 3 therapy had a poor outcome (p=0.028). or 4 leukopenia associated with chemotherapy in 78 lung cancer patients (age: 43 to 82 (1) Gerson S.L. et al: Discriminant Scorecard for Diagnosis of Invasive y.o, mean 65 yr.s) were entered. Patients Pulmonary Aspergillosis in Patients with Acute Leukemia. Am J Med were randomized to receive TMS lg BID or TMS 79:57-64 (1985) plus NFLX 200mg TID unti 1 WBC count 334

recovered to >2000/mrr~ . The primary endpoint years: infections due to Gram-negative pathogens have was occurrence of fever of>_38~ Episodes shown a steady decline while Gram-positive bacteria have were judged not evaluabie when patients got gained a most important role, adding up to an approximate febrile within 24 hours of start of therapy; 63% as indicated in EORTC trials, showing an overall 28% 127 episodes,were evaluated (64 for TMS and increase in opportunistic cocci (Staphylococcus 63 for TMS plus NFLX). Fever occurred in 10 (16~ episodes in the TMS arm and 2 (305) in epidermidis, Streptococcus viridans). Consequently, the TMS/NFLX arm (p=0.03). Nadir WBC and antimicrobial regimens have changed in order to obtain neutrophi I counts, duration of -->grade 3 better control of infections in such pts. This paper reports leukopenia or neut ropenia and the usage of the results of a study started in 1991 usingthe triple GOSP were not significantly different combination vancomicin + imipermm-pefloxacin. Up to now between the 2 arms. We concluded that NFLX 26 pts with granulocytes < 500 /mm 3 and fever > 38~ plus TMS is more effective in prevention of have been treated with this regimen, using the following neutropenic fever in lung cancer patients. schedule: vancomycin 30 mg/m2/day i.v. every 12 hrs, imipenem 1500 mg/day i.v. every 8 hrs, pefloxacin 800 mg/day i.v. every 12 hrs. The types of infection treated . BLOOD LEUKOCYTE DNA POSTRADIATION have been: FUO 12 (46%), lung 8 (30%), skin 2 (8%), REACTION DURING RADIOTHEPAPu OF septicaemia 2 (8%), bladder 1 (4%), gastro-entedfis 1 (4%). PATIERTS WITH HODGKIR'S DISEASE No important side effects nor hypersensitivity reactions or ~S. Ivanov, Ph.D., L. KorYtova, Prof, haematochemical alterations have been observed. H. Ilyin, H.D., L. Malysheva Following this regimen a clinical response was observed in Centr. Pes. lnst. of Roentgenology & 22 (84%) pts while, no response was observed in 4 (16%) RadiologY, St.-Petersburg, Russia pts; time to defervescence was obtained within 3 days in 70% of pts. These results show an high response rate for The investigation goal is to use the early this triple combination antimicrobial regimen with complete postradiation blood DNA content changes du- remission of both symptoms and signs of infection in most ring radiotheraPY (RT) of cancer for the pts. prognosis of the subsequent leu~oPenla va- lue. The patlents of H-~ sta~es HodEEin's disease treated at the LAE-15 MeV by usual 0 CORYNEBACTERIUM JEIKEIUM SEPSIS IN fractlonation to total dose 40 GY. The DNA HAEMATOLOGICAL PATIENTS. content was fluorometrically determined (by *Hans van der Lelie, MD (i), 6-diamidlno-2-phenyllndole) in 0.02 ml of Maurine Leverstein-Van Hall (2) and blood before treatment, then in 2~h after Ed Kuijper, MD (2). the 1st dose, In the middle and end of PT. Academic Medical Center, University Retrospective analysis of obtained data de- of Amsterdam, department of monstrated, that the I-st Paiients s ha- internal medicine, division of haematology (I) ring at the end PT the blood leukocyte le- and department of medical microbiology (2), PO vel below 3xlOS/l, had about a-tlmes decre- Box 22700, 1100 DE Amsterdam, The Netherlands ase of the DNA concentration after the Ist irradiation Inthe 6az of cases. This early decrease of DNA content was conditioned by the granulocYte nuclear material. The bio- We report three patients with Corynebacterium chemical change was not- accomPanied bY the jeikeium sepsis in the neutropenic phase of proportional decrease of the leukocytes their treatment for acute myeloid leukaemia. number. The H-nd Patients grou~, having no Fever was the first symptom. All three had a le]~openla at the end of RT, revealed the central venous catheter which was removed. Two blood DNA concentration decrease only after patients developed subcutaneous nodules the middle of treatment course. The DNA con- containing pus when the neutrophil count tent ~all at the middle and the end of RT recovered; one had intracutaneous- and was conditioned bY both lYmPhocYtes, and pulmonary lesions. They were treated with granulocYtes. These changes were not Prac- vancomycin and recovered at the moment their tically connected with the plasma changes. neutrophil count started to rise. Our review Thus given biochemical criterium may be of 80 neutropenic patients with C jeikeium used as a sensitive and express index for sepsis reported in the literature together the early prognosis of leukopenia value. with our 3 cases indicates that risk factors for infection are the presence of a central 9 venous catheter, being an adult male or postmenopausal female, profound and prolonged TRIPLE COMBINATION ANTIMICROBIAL REGIMEN IN neutropenia and exposure to multiple THE TREATMENT OF INFECTIONS OF NEUTROPENIC CANCER PATIENTS antibiotics. Skin lesions are reported in 48%, *A. Casali, T. Gionfra, S. Santini, F. Pignatti, M. Lopez. pulmonary lesions in 36%. The overall Istituto Regina Elena, Rome, Italy. mortality is 34% but in patients with recovery of the bone marrow only 5%, Therefore hemato- The incidence of bacterial infections in neutropenic cancer poietic growth factors should be considered in patients (pts) has changed progressively over the past 10 case of infection caused by C jeikeium. 335

"1 1 AMBULATORY MANAGEMENT OF VARICELLA- Cost: The potential cost savings are substantial; during a 3-month study, ZOSTER VIRUS (VZV) INFECTION IN IMMUNO- 165 pts without toxicity who were not chosen for monitoring by RM were monitored by CLIN, a projected $148,000 savings/yr. (payer's perspective). COMPROMISED CANCER PATIENTS Not included in this egtimate are the costs of managing the nephrotoxicity *Kenneth Rolston, M.D., Ellen Manzullo, M.D., of pts who could have been identified by RM but were not monitored by Edward Rubenstein, M.D., Susan Frisbee-Hume, CLIN. 3 of these pts developed serious toxicity; 1 required dialysis. R.N., Saul Rodriguez, M.D., Linda Elting, Dr. P.H. Implementation: Successful implementation of this strategy requires MD Department of Medical Specialties, The University of Texas M.D. agreement, but very little action on their part. Because of the simplicity of Anderson Cancer Center, Houston, Texas, U.S.A. the model, a pt's risk of nephrotoxicity can be calculated by the dispensing Immunocompromized patients with VZV infections are generally pharmacist without MD input. Serum level monitoring could then be initiated using either standardized orders or reminders to MDs. hospitalized, confmed to strict isolation rooms, and treated with Conclusion: Improving outcomes to patients and simultaneously saving intravenous acyclovir for 10-14 days. This approach is effective but resources is a dominant strategy which will be implemented at our center in expensive and consumes valuable resources. We treated 39 patients the near future. with VZV infection who were clinically stable in an open trial of outpatient acyclovir therapy. tdw'~ HEPATITIS VIRUS INFECTIONS IN PEDIATRIC Results: There were 27 women and 12 men with a median age of 52 4 ONCOHEMATOLOGICAL PATIENTS WITH LIVER years. Lymphoma (10) and leukemia (10) were the most common DISEASE *E.V.Samochatova, M.D., A.A.Maschan, M.D., underlying malignancies, and 8 patients had undergone BMT. Five O.V.Konlikova, M.D., M.V.Timakova, M.D., received corticosteriod therapy and 4 received localized radiation N.R.Tjukalova, M.D., M.A.Getmanova, M.D., therapy. Head and neck (10) and truck (8) lesions predominated and 6 M.I.Mikhailov, M.D., A.G.Rumjantsev, M.D. patients had cutaneous dissemination of lesions. 34 patients (87%) Research Institute for Pediatric Hematology Moscow, Russia. were successfully treated without hospitalization. Failures included 2 patients admitted for transient renal insufficiency, 2 with progressive To assess the occurrence of viral infection as a cause of hepatitis 36 VZV which required combination antiviral therapy, and one with a children with clinical and laboratory symptoms of liver disease during the treatment for acute leukemia (AL) and acquired aplastic anemia bacterial superinfection. One patient relapsed but was successfully (AA) were systematically tested for full panel of specific markers of retreated with outpatient acyclovir. The median length of therapy was hepatitis B (HBV) and C (HCV) virus infection. Such investigations were made for the first time in Russia. - 8 days. Patient compliance and satisfaction was high and there were Patients. 36 pts (18 boys 18 girls aged 2-17 yrs, mean 9 yrs) with no dropouts from the ~tudy. elevated alanine amino transferase (ALT) level were studied during Conclusions: Clinically stable immunocompromized patients with different phases of AL (32 pts) and AA (4 pts) treatment included. All pts had received multiple transfusions of blood derivates. Blood from VZV can be safely treated without hospitalization. Identification of a volunteer donors were routinely checked up only for presence of low-risk subset among these patients should be attempted, since such HBsAg. 4 AA pts were receiving cyclosporine A; AL pts (13 pts with low-risk patients might be safely managed with sequential (intravenous ALL, 5 pts with AML) were on the intensive phase of antileukemic therapy, 10 pts (9 ALL pts, 1 AML pt) - on the maintenance followed by oral) or oral antiviral regimens, now that potent oral drugs therapy and 4 pts were off treatment. Before the presented investigation (famciclovir, valaciclovir) have become available. These measures all pts were tested for HBsAg and 3 pts for HCV-antibodics (by the 1-st generation of ELISA). HBV-infection was found in 14 pts, HCV in 2 might further reduce costs and increase the ease of administration of pts; 20 pts (60%) were presumed to have toxic hepatitis. antiviral therapy. Methods. ALT level, serologic markers of HBV (HBsAg, HBcAg, HBeAg, anti-HBsAg, anti-HBcAg, anti-HBcAg IgM and IgG, FIBeAg), and HCV-antibodies, HCV RNA, Serology was done with commercial ELISA tests, HCV RNA detection- by polymerase chain reaction (PCR) 1 2 FROM RESEARCH TO POLICY: APPLYING A (Amplieor HCV, Roche). PREDICTIVE RISK MODEL FOR VANCOMYCIN Results. 28 (78,8%) of the 36 pts studied had evidence of exposure to MONITORING. *Danna Kurtin, M.P.H., Linda Elting, viral infection: 9 had markers of HBV infection, 10 anti-HCV and/or HCV-RNA. 10 pts were positive for both. HBV and HCV. Only 7 pts Dr.P.H., Kenneth Rolston, M.D., Gerald Bodey, M.D., (22%) with elevated (>2 ttmes up to normal) ALT level had no HBV or Edward B Rubenstein, M.D. The University of Texas MD HCV markers. There were various combinations of HCV tests: Anderson CanccrCenter, Houston, TX, USA. seropositivity or negativity with RNA-positivity, PCR-positivity without Translation of the results of health services research antibodies. Different combinations of HBV markers were revealed: HBsAg + HBeAg + anfiHBc, only HBsAG, only antiHBc. 4 pts had into clinical practice is a challenge for policy makers. Major alterations of HBsAg + anti HBsAg simultaneously. The number of transfusions in pts physician's (MD) behavior or clinical decision-making may bc required. with viral hepatitis varied strikingly (3-98 transfusions). Occasionally however, a treatment strategy is identified that provides Conclusions. It is possible to detect the appearance of hepatitis virus superior outcomes at a reduced cost with little necessity for alterations of infection in immunocompromised children with oncohematological diseases using appropriate methods. The prolonged follow-up is major practice patterns. We have identified such a strategy for monitoring necessary to assess relationship of HVI during intensive treatment of serum levels among cancer pts receiving vancomycin (vanco). oncohematological diseases with development of chronic liver disease in The Strategy: A risk model (RM) employing data available at the onset of pts after treatment withdrawal. vaneo therapy (APACHE III score, concurrent drugs, and estimated creatinine clearance) was developed to predict vanco-associated nephrotoxicity among lots with cancer. It (1) identifies pts with high risk of 14 PULMONARY INFILTRATES AETIOLOGY IN vanco-associated nephrotoxicity; (2) permits early monitoring and LEUKEMIC PATIENTS WITH FEVER intervention in high-risk pts; (3) provides an opportunity for decreased Ji~ Vorli~ek,M.D.,Jana Sk~i~kov~,M.O.T resource utilization by identifying pts with low risk of nephrotoxicity; and Ji~ Mayer,M.O. (4) can lead to cost-effective monitoring strategies. Oept.of Medicine Masaryk University Effectiveness: Comparing the specificity of the RM to clinician-based Hospital,Brno, Czech Republic monitoring (CLIN3 in the validation study, RM (90%) was far superior to *Oept.of TB and Respiratory Oiseases, CLIN (73%; P= 0.01). More importantly, of 59 pts who developed toxici~', Babice nad Svitavou, Czech Republic RiM chose 49 to monitor compared with only 36 by CLIN (Sensitivity, 83% vs 61%, respectively; P < 0.01). Of 8 pts with severe toxicity, RM chose 8 In the course of 4 years fiberoptic bronchoscopy with (100%) to monitor vs only 5 (63%) by CLIN (P = 0.07). bronchoalveolar lavage (BAL) was indicated in 75 pa- 336

tients with leukemias to clarification of the pulmo- IV DOLASETRON (DM) Vs IV nary infiltrates aetiology. BAF was examined cytolo- 16" METOCLOPRAMIDE (M) IN EMESIS gically and microbiologically. 34 (45.5~) patiemts PREVENTION AFTER CISPLATIN were suffering from acute myeloid leukemia,13(17.3~) CHEMOTHERAPY (CT). *B. Chevallier, from acute lymphoblastic leukemia, 15 (20.0~) from P. Cappelaere, T. Splinter, M. Fabbro, N. chronic myeloid leukemia and 13 (17.3%) from chronic Claverie, et al. Centre Henri Becquerel, lymphatic leukemia. On the bases of the BAF examina- tion the aetiology of pulmonary infiltrates was pro- Rouen, France; Centre Oscar Lambret, Lille, ved in 69 (92.0~) patients. In 2 (2.7~) patients My- France; University Hospital Lijkzigt, cobacterium tuberculosis and in one (1.3~) patient Rotterdam, Netherlands; Centre Val Legionella were cultured from BAF. In &6 (61.3~) pa- d'Aurelle, Montpellier, France; MMD, tients other bacterias were obtained. The presence of Strasbourg, France. fungi was proved in BAF in 24 (32~) patients. In 8 In this double-blind, comparative trial, 226 cancer patients were (i0.8%) of those fungi were found only microscopica- lly, in ii (14.7~) was cultured Candida albicans, in randomized to DM (1.2 mg/kg or 1.8 mg/kg, 15 minute one (1.3~) Rhizopus, in one (1.3%) Aspergillus fumi- infusion 30 minutes prior to CT) or M (4 mg/kg continuous gatus, in one (1.3~) Cephalosporium, in one (1.3%) infusion for 8 hours after a 3 mg/kg loading dose) to prevent Candida pseudotropicalis and in one (1.3%) Candida emesis caused by cisplatin (>80 mg/m2). Results for complete krusei. Viruses were proved in BAF in 6 (8~)patients. response (CR = 0 emetic episodes, EE, and no rescue medica- In 3 (4.0~) patien;s Herpes simplex virus and in 3 tion, RM); CR + major response (CMR = 0-2 EE's and no (4~) Cytomegalovirus. Pneumocystis carin~i was found RM); and median time (hrs) to first EE or RM (MTEE) appear in BAF in 14 (18.7g) patients. On the basis of the cy- below. tological examination blasts were found in BAF in 33 (44~) patients, alveolar haemorrhage was proved in 4 DM (1.2) DM (1.8) M p value p value (5.3g) patients and diagnosis ARDS was established Response (n=84) (n=72) (n=69) 1.2 v M i 1.8 v M in one (1.3%) patient. In 55 (73.3~) leukemia pa- CR 40 (48%) 41 (57%) 24 (35%) .0058 .0009 tients pulmonary infiltrates have diasappeared after treatment based on the BAF examination. CMR 47 (56%) 53 (74%) 43 (62~ .969 .065 MTEE 22.50 hr > 24 hr 5.50 hr .0003 .000i

~ INFECTION PREVENTION BY SELECTIVE DECONTAMINATION IN Investigator assessment of nausea severity and global efficacy CItlLDREN UNDERGOING BONE showedthat DM 1.8 and 1.2 mg/kg were superior to M (p<.05). MARROW TRANSPLANT DM 1.8 and 1.2 mg/kg, respectively were superior to M for patient visual analog scale satisfaction, and DM 1.8 mg/kg * Shamvil Ashraf, M.D., Caroline Osbourue, approached significance (p=,076)vs M. The most common MR Pharm S, Rick van Sacne, M.D., Lynn Ball, M.D. adverse event with DM was headache (15 %). No extrapyra- midal signs were recorded with DM; (1 patient for M). DM Dcpt tlaematology/Oncology, Pharmacy and (1.8 and 1.2 mg/kg) was more effective than M in preventing Med Microbiology, emesis related to cisplatin chemotherapy. Royal Liverpool Children's NHS Trust, Liverpool LI2 2AP, UK.

The first 50 BMT's at the Royal Liverpool Children's NHS Trust [Alder Hey] were performed between April 1987 and October 711r RANDOMJ~ED,DOUBLE-BLIND, pARALLEL TRIAL 1994. The aim of this report is to evaluate SDD during the first OF THE ANTIEMETIC EFFECT AND TOLERABILI- post-BMT month in this series of 23 allografls, 22 autografts and TY OF GRANISETRON (GILA) VS PREDNISOLONE (PILED) PLUS TItE DOPAMINE D~ANTAGONIST 5 matched unrelated donors. SDD is a method used to abolish METOPIMAZINE (MPZ) IN 223 WOMEN WITH carriage of potentially pathogenic microorganisms [PPM] BREAST CANCER RECEIVING MULTIPLE CYCLES including yeasts, S.au.reu.s and Gram-negative bacilli [GNB]. The OF MODERATELY EMETOGENIC CHEMOTHERA- first 25 BMTs received oral neomycin, colistin [polymyxin E] and PY*T Sigsgaard,(CT). -' -J "^~t~attl~ ~~ cu ' ,~I I Andersen 2, H Havsteen 3", nystatin [NEOCON] with chlorhexidine mouth wash, whilst the M Kj~e~, P Dombernowsky '. Depm*t.ments of Oncology, second series of 25 BMTs were given oral polymyxin E, 1. Copenhagen University Hospital Herlev, 2. Aalborg tobramycin and amphotericin B [PTA] in both gel and suspension. Hospital, 3. Vejle Hospital, Denmark. From October 1992 to Au~qlst 1994 223 CT-naive stage I or II bre~t cancer The efficacy of SDD was significantly higher in the children patients (!~s) were randomised to receive a single dose of GRA 3 ms i.v. p~or receiving PTA compared with NEOCON,at both oropharyngeal to chemotherapy (112 pts) or a 3 day oral treatment with PLIED 25 mg plus and gastrointestinal level [88% vs 33%; p<0.01]. A septic MPZ 30 mg prior to chemotherapy followed by PRED 25 .rag day.2 an d 3 PlloUS_ MPZ 30 mg q.i.d. (111~). Two hundred and four ~ recelveo anjuvant cyc o- response was seen in 76% and 86% of the children on NEOCON phosphamide 600 mg/m~ (CTX) plus methotrexate 40 mg/m pros z-nuoroura~ and PTA, respectively. One third of the patients developed oil (5-FU) 600 mg/m~ (CMF) and 19pts received adjuvant CTX 600 rag/m- septicaemia [indigenous Gram-positive cocci only] in both groups. plus epirubicin 6Omg/m~ plus 5-FU 600 mg/m2 (CEF). A low carriage index for the target PPM during the study All pts were scheduled to receive 9 identical cycles of CMF or CEF given every 3 weeks. Pts received the same antiemetie treatment during all 9 manoeuvre of SDD was associated with negative blood cultures courses of CT but were withdrawn if they had ~_ 5 emetic episodes during [p<0.01]. Acute GVHD of moderate or greater intensity any day on day 1-5 after CT or if they were not satisfied with the antiemetic [ > grade If] occurred in nine recipients [9 of 28 allografts and treatment during any of the cycles of CT. The median number of CT cycles completed with GRA was 5 (95%confidence matched unrelated donors = 32%]. It is concluded that interval 4-6) compared with 2 (95% confidence interval 2-2) for PRED + septicaemia from yeasts and GNB, but not the septic response, MPZ. The number of CT-cydes completed with GRA was significantly h~gh~r were successfully prevented by SDD. than the number completed with PRED + MPZ (log-rank test, P=0.0U2 ). 337

Maintance of emetic control. Courses 1-9. 1 9* SINGLE ORAL DOSES OF DOLASETRON 1.2 VERSUS MULTIPLE DOSES OF 1.1 ONDANSETRON IN PREVENTING EMESIS t.0 AFTER MODERATELY EMETOGENIC .9 CHEMOTHERAPY. *A Del Favero, J Bergerat, A Chemaissani, H Dressier, et al. Istituto Medicina Interna, Perugia, Italy; ~ .5 Hopitaux Universitaires de Strasbourg, France; A ~ ~=='-L - -"1.._. I- ..... =t Lungenklinik des Stadtkrankenhaus, Ktln- 3 Merheim, Germany; MMD, Rtisselsheim, Treatment group ,2 Germany. I GRA 0.0 PREO+ MPZ This double-blind trial assessed the comparative antiemetic 1 2 3 4 5 6 7 8 9 efficacy of dolasetron mesilate (DM) and ondansetron (eND). At 26 study sites, 398 cancer patients were randomized to 25, 50, Courses ofchemotherapy 100, 200 mg DM or eND (8 nag x 4; 8 mg x 3 at four centers) prior to receiving IV chemotherapy (CT) principally with cyclo- In conclusion a single dose of GRA i.v. was superior to 3 days of oral treatment with PLIED + MPZ. Furtermore the antiemetic efficacy of both phosphamide (>-600 mg/m2), doxorubicin (>_40 mg/m2), or treatments declined during multiple cycles of CT. The study was decoded carboplatin (>-300 rag/m2). Efficacy was measured using com- May 1995. Data analysis is still ongoing and a complete analysis will be plete response (CR: 0 emetic episodes rEEl and no rescue medi- presented. cation [RM]); CR+ major response (CMR: 0-2 EE and no RM); and patient reports of nausea severity (A from baseline to 24 hours) and satisfaction (at 24 hours) on a 100 mm visual analog scale (VAS). At 24 hours, a linear trend with close was statisti- cally significant across the 25, 50, 100, 200 mg doses of DM (p<.0001) both for CR (45.0%, 49.4%, 60.5%, and 76.3%), respectively, and for CMR. The CR rate for eND was 72.3%. 18" ONDANSETRON VS GRANISETRON, BOTH CR and CMR rates were equivalent for DM 200 mg and eND. COMBINED WITH DEXAMETHASONE IN THE Linear trends were significant for median time to first EE/RM, PREVENTION OF CISPLATIN-INDUCED EMESIS. for patient VAS nausea-severity ratings, and for the combined * F Roila, M V. De Angelis, M.D., F. De Marinis, M.D., G. Scarfone, M.D., G. Scagliotti, M.D., D. parameter of CR + no nausea (<5 mm VAS), (p<.0001 for all Donati, M.D., A. Santoro, M.D M.C. Locatelli, M.D., parameters). Median change in VAS nausea-severity scores E. Sansoni, M G. Matera, M.D., C. Fava, M were 3.5 mm and 0 mm with the 100 mg and 200 mg DM doses, for the Italian Group for Antiemetic Research. compared to 3 rnm with eND. VAS satisfaction scores were 92, 99, and 98, respectively, with DM 100 and 200 mg and eND. From December 1992 to July 1994, 973 consecutive patients DM and eND were well tolerated There were no significant scheduled to receive for the first time cisplatin at doses >__ 50 trends with dose for adverse events with DM. We conclude that mg/m 2, used alone or in combination with other antineoplastic a single oral dose of DM 200 mg is equivalent to multiple dose agents, entered a double-blind multicenter randomized study eND in preventing nausea and emesis after moderately comparing ondansetron (eND) 8 mg iv vs granisetron (GRAN) emetogenic CT. 3 mg iv, both diluted in 50 ml normal saline and administered in 15 minutes, 30 minutes before chemotherapy. Dexamethasone (DEX) 20 mg iv was added to the 5-HT 3 antagonists and administered in 15 min, 45 rain before chemotherapy. "k IIIGII-IDosE CYSPLATIN (|[D-CDDP) INDUCED EMESIS: For the prevention of delayed emesis, during day 2-4 after 20 TIlE RULE OF 5-|1T3 RECEPTOR ANTAGONISTS (5UT3- chemotherapy, all patients received metoclopramide 20 mg 4 RA), DEXAMETItASONE (n) AND METOCLOPRAMIDE (M) *l,uigi Currcli, M.D., Alessandro 13iaochi, M.D., Massimo Ghiani, times/day + DEX 8 mg im x 2 on day 2-3 and 4 mg im x 2 on M.D., Biaoealosa Lampis, M.D., Luciana Cuatini, MD., and day 4. The assesment of nausea and vomiting was done for 6 Giovanni Mantovani, M.D. consecutive days after chemotherapy. Dept. of Medical Oncology, Univcrsity of Cagliari, 09124 Cagliari, 966 patients (483 receiving eND + DEX and 483 GRAN + Italy DEX) were evaluable for intention to treat analysis. Patient Nausea and vomiting ure tile major dose-limiting side.effects for a number of cytostatic drugs, particularly IID-CI)I)P. Potent 5-ITT3- RA have bceo sho,ml to prevent acute characteristics were well balanced between the two antiemetic nausea and vomiting when given with cylostatic treatment, but the evidence for thcir treatments. Complete protection from acute vomiting/nausea etlicacy in the prevention of delayed symptoms is sparse. D sinewed antiemetic activity was obtained in 383 (79.3%)/348 (72.0%) of patients receiving when used alone for pts receiving non cysplatin (CDDP) chemolherapy, tligh dose M eND + DEX and in 386 (79.9%)/347 (71.8%) of those activity in preventing acute symptoms of tlD-C1)DP is well documented. The aim of our open randomized study was A) to compare granisetron (GllA), ondansetron (eND), receiving GRAN + DEX. Complete protection from delayed tropisetron (TRO) in the profilaxis of acute nausea and vomiting induced by highly vomiting/nausea (day 2 to 6) was obtained in 69.7%/52.9% emetogeuic chemotherapy (80-100 mg/sqm of CDDP on day I); B) to compare the and 70.0%/49.6%, respectively. association between D mid low dose M versus 5-HT3-RA (GILA, eND, TRO) in preventing delayed nau~a m~d vomiting in cancer patients (pts) receiving high dose CDDP Adverse events were mild and not significantly different (80-100 mg/sqm) on day 1 were evaluated. As for A) GRA (3 mg i.v.), eND (24 mg i.v.) between the two antiemetic regimens. aud 'FRO (5 mg i.v.) were given at a single dose prior to administration of CDDP. 179 pts In conclusion, eND 8 mg and GRAN 3 mg, both combined with (170 men and 9 Women, mean age 58.2 years, range 31-78 ; PF ECOG 0-2), 169 (7 St 1], 45 St 1Ii, 117 St IV) with head and neck cancer, 5 ( 1 St I11, 4 St IV) with esophageal DEX, showe d similar efficacy and tolerability in the prevention cancer, 2 with melanoma St 1V, 3 with hmg cancer St tV were includcd in the study. 667 of acute and delayed cisplatin-induced emesis; therefore, the chemotherapy cycles were evaluated: 233 for GRA, 206 for eND, 228 for "FRO. At the choice between them should be made on the basis of slart of first chemotherapy cycle pts were randomly assigned to one of three antiemetics and prosecuted the following dlemotherapy cycle with the same antiemetic coverage, acquisition costs. mdess experienced a failure (F): in this last case the pt was crossed-over randomly to one Supported by A.U.C.C. (Associazione Umbra Centre il Cancro). of the oilier two antiemetics, hi case of further F, the pt was assigned to the third 338

anfiemetie drug. In such a way 31 pts were crossed over to a second antiemetic and 3 te DOLA~ETRON (DOL) VS ONDANSETRON (OND) the third antiemefic drug. The treatment groups were well matched in terms of age, 22* WITtt AND WITHOUT DEXAMETHASONE (DEX) gender. PS and stage of disease. Verbal informed consent was requested to all pts All'pts IN THE PREVENTION OF NAUSEA (N) AND included in the study had net received previous chemotherapy.Results were as fellows: GIlA complete response (CR) 170/233 (73.0%), major response (Mall) 37/233 (15.9%), VOMITING (V) IN PATIENTS (PTS) RECEIVING minor response (MiR) 11/233 (4.7%), failure (F) 15/233 (6,1%); ONI) CR 1551206 MODERATELY EMETOGENIC CHEMOTHERAPY (75.2%), MaR 36/206 (17.5%), Mill 5/206 (2.4%),'F 10/206 (4.9%); TRO CR 154/228 (MEC). *WS Lofters, B Zee, for the Symptom (67.5%), MaR 39/228 (17.1%), MiR 21/228 (9.2%), F 14/228 (6.2%). There was no statistically significant difference between GRA, OND and TRO for CR, nmjor efficacy Control Committee of the National Cancer Institute of (CR+MaR) or F. Adverse effects were not reported. As for B) D (8 mg i.m.) was given Canada Clinical Trials Group and Nordic Men'ell Dow every 12 h and M (20 mg p.o.) was giveu every 6 h; 5-HT3-RA(GRA 2 mg on d2-d3, 1 Research Canada, Queen's University, Kingston, mg d4-d5, or OND 16 mg d2-d3, 8 mg d4-d5 or TRO 5 mg d2-d5). 12 pts (11 men and I Ontario, Canada K7L 3N6 women, mean age 54.2 years, range 38-77; PF ECOG 0-1), all (1 St 1ii, tl St IV) with head and neck cancer. 29 chemotherapycycles were evaluated: 21 for 5-Ifr3-RA and 8 for M p73 plus D. At the start of first chemotherapycycle pts were randomly assigned to one 703 pts were enrolled in a randomized, multicentre, double-blind 2X2 of three 5HT3-RA for acute nausea and vomiting, while for delayed symptoms factorial design trial to compare after MEC the acute efficacy and safety of randomization has been done between the same 5HT3-RA being administered for acute a single IV dose of DOL (2.4 mg/kg) vs 32 mg OND IV, mad to evaluate the nausea and vomiting and M plus D, pts prosecuted the following d~emotherapycycle with additive effect of IV DEX with each drug. In 555 pts DOL (200 mg daily) the ~me autiemetie coverage, unless experienceda failure (F). Results were as follows: 5- I rr3-RA complete response (CR) 12/21 (57.1%), major response (MAR) 9/21 (42.9%); M or OND (8 mg bid) +/- DEX (8 mg daily) were continued orally for 6 days plus D CR 5/8 (62.5%), MaR 3/8 (37.5%). Our prelinfinarydata fail to show statistically for protection from delayed N/V. Pts receiving 3 days of MEC were given significantdifference. Adverse effects were not reported. IV OND or DOL +/- IV DEX for 3 days and oral drugs for 4 days, Pts recorded episodes of vomiting mad assessed the severity of their nausea on a VAS scale in a daily diary. Pts who failed to report N and V for an interval were considered for the purposes of this analysis to be treatment failures with respect to control of vomiting. The calculation of mean nausea severity 21" DOUBLE-BLIND COMPARISON OF THE omitted missing intervals. Results: Of 696 eligible pts 71% were female, ANTIEMETIC EFFICACY OF TWO SINGLE 51% had metastatic disease, 44 % received doxorubicin and 22 % < 50mg/m2 IV DOSES OF DOLASETRON AND ONE IV cisplatin. 197/343 (57%) DOL pts had complete protection (CP) over 24 DOSE OF GRANISETRON AFTER hours vs 236/353 (67%) OND pts (p=.013). Mean nausea severity scores CISPLATIN (_>80 mg/m ~) CHEMOTHERAPY. (MNS) were 13.1 and 10.1 (p=.051) for DOL and OND respectively. *B Audhuy, P Cappelaere, N Claverie, et al. 271/402 (67%) DEX pts had CP vs 162/294 (55%) without DEX (p< .001). Hopital Louis Pasteur, Colmar, France; MNS were 8.1 and 16.3 (p<.001) with and without DEX. At 7 days, Centre Oscar Lambret, Lille, France; MMD, however, DOL and OND had virtually equivalent results (CP 36 % vs 39%, Strasbourg, France. p=.459), (MNS 11.0 vs 8.9, p=.076) but the effect of DEX was greater (CP 48% vs 28% p<.001), (MNS 6.4 vs 13.0, p< .001). All drugs were To assess the comparative efficacy and safety of dolasetron well tolerated. Conclusion_. At a 2.4 mg/kg dose DOL is less effective in mesilate (DM) and granisetron (G), 476 cancer patients at 29 controlling immediate post MEC N and V than 32 mg OND. OND and DOL centers were randomized to 1.8 or 2.4 mg/kg IV DMor G (3 are not demonstrably different over 7 days. DEX adds efficacy to both mg), 30 minutes prior to administration of _>80 mg/m 2 IV drugs. cisplatin chemotherapy (CT). Gender and previous CT were used to stratify patients into four groups: male CT-naive and non-naive and female CT-naive and non-naive. Antiemetic PERSISTENCE OF EFFICACY OF THREE efficacy was compared using complete response (CR: 0 emetic 23* ANTIEMETIC REGIMENS AND PROGNOSTIC episodes [EEl and no rescue medication [RM]) and CR + major FACTORS IN PATIENTS SUBMITTED TO response (CMR: 0-2 EE and no RM). Efficacy was also as- MODERATELY EMETOGENIC CHEMOTHERAPY sessed using median time to first EE/RM, patient ratings of * E. Bailatod, PhD, F. Roila, M.D., V. De Angelis, nausea and satisfaction via a 100 mm visual analog scale (VAS) M.D., E. Carnpora, M.D., F. Cognetti, M.D., R. Sabbatini, M.D., D. Donati, M.D., S. Ricci, M.D., F. and physician assessment of nausea severity and global efficacy Salvati, M.D., G. Catalano, M.D., F. Di Costanzo, on a discrete scale (DS: none, slight, good, excellent). CR rfftes M.D., for the italian Group for Antiemetic Research. were 54%, 47%, and 48%, respectively, for DM 1.8 and 2.4 mg/ kg and G. CR rates for both DM doses were statistically equiva- Purpose. To evaluate antiemetic efficacy and tolerability of granisetron, lent to G. Comparisons of CR rates between DM 1.8 mg/kg and de• and their combination, over repeated courses of G (p=.0893) and between the two DM doses (p=.0602) were not moderately emetogenic chemotherapy (cyclophosphamide, 600-100 statistically significant. Results from CMR, median time to first mg/m=, doxorubicin, z 50 mg/m2, epirubicin, ~ 75 mg/m=, or carboplatin, _> EE/RM, patient VAS assessments, and physician DS ratings 300 mg/m =, either alone or in some combination) and the influence of the further confirmed the equivalence of DM 1.8 and 2.4 mg/kg and prognostic factors on occurrence of nausea and vomiting. G. The efficacy of DM 1.8 and 2.4 mg/kg and G was similar Patients and methods. 428 consecutive cancer patients entered a across each of the four patient strata. Headache (~ 25%) was the multicentre, randomized, double-blind study comparing granisetron 3 mg most frequently reported adverse event with DM and G, and intravenously, dexamethasone 8 mg intravenously and 4 mg orally every hours for four doses, or the combination of dexarnethasone plus there were no statistically significant differences in incidence of six granisetron at the same doses, administered for three consecutive cycles. adverse events between treatments. We conclude that DM at Occurrence of nausea, retching and vomiting was monitored during 24 hrs doses of 1.8 and 2.4 mg/kg is equivalent to G in preventing after chemotherapy administration by a diary card. nausea and emesis induced by _>80 mg/m 2 cisplatin. Resu/ts. 398 patients wore evaluable for clinical efficacy at first, 354 at second, and 322 at third cycle of chemotherapy. Dexamethasone plus granisetron induced significantly greater complete protection from vomiting / nausea / nausea and vomiting than granisetron alone in all three cycles, while, with respect to dexamethasone alone, complete protection from vomiting was significantly greater at first and second cycle, and complete protection from nausea, and from both nausea and vomiting only at first 339

cycle. Complete protection did not differ significantly among the three MEC were randomized to continue DEX at 8 mg po daily or DEX plus the cycles in patients receiving dexamethasone plus granisetron or 5HT3 (DOL 200 mg daily or OND 8 mg bid). Pts receiving 3 days of MEC dexamethasone alone, while it decreased significantly, at least for were given IV drugs for 3 days and oral drugs for 4 days. Pts recorded vomiting, in patients receiving granisetron alone. Protection obtained in the episodes of vomiting and assessed the severity of their nausea on a VAS scale previous cycle of chemotherapy was the most important prognostic factor in a daily diary. Pts who failed to report N and V for an interval were in the occurrence of nausea and vomiting, considered for the purposes of this analysis to be treatment failures with Conclusion. The combination of dexamethasone plus granisetron offers the respect to control of vomiting. The calculation of mean nausea severity best antiemetie protection because of its greater efficacy with respect to the omitted missing intervals. Results: 72 % pts were female, 50 % had metastatic other two regimens at first cycle, and because its activity is maintained in disease, 43 % received doxorubicin, and 22 % had < 50 mg/m2 cisplatin. Over the subsequent cyetes of chemotherapy. 7 days 58/141 (41%) pts on DEX alone had eompIete protection vs 123/261 (47%) on DOL + DEX or OND + DEX. This difference was not significant (p=.471; 90% CI -3% to 15%) when, as planned, both 5HT3s were combined in a stratified comparison. There was a significant reduction in USE OF ~RANISETRON (G) AND DEXAMETHASO- nausea severity (9.2 vs 6.4; p=.030) in the combined 5HT3 added group. 24* NE (D) ON DAY 2-7 FOLLOWING HIGH DOSE Conclusion: Routine addition of 5HT3s to "DEX beyond 24 hours in pt s CISPLAIIN (HDCP) *Jean Latreille, receiving ME(] reduces N but has no significant impact on V. Further D/anne 3ohnston, Francis Laberge, Dave analyses are required to determine if this benefit justifies the cost of these Stewart, James Rusthoven, Laurie Nishi- drugs. mura, Joe Pater, Benny Zee, National Cancer InstiLute of Canada Clinical Trials Group, Kingston, Ontario, Canada and SmithKline Beecham Pharma. Ibis randomized double-blind multicenter Lrial compa- TROPISETRON FOR TREATMENT OF CHEMO- red G alone X 7 days to G+D on day I followed by D or 26* THERAPY INDUCED NAUSEA AND VOMITING: G+D on day 2-7. Our objectives were to study the ad- RESULTS OF A SWISS OPEN MULTICENTER STUDY ded effect of D on day I and to evaluate which combi- R. Joss1, M.D., C. Sessa2, M.D., *K. Bused, M.D., nation was more efficacious on day 2-7. Of the 550 U. Kreuter4 and V. Grimaudo5, M.D. / Oncology Dpts KS patients (pts) registered, 13 were ineligible and 4 Lucerne1, OSG Bellinzona~, Inselspital Berne~, Consult AG inevaluable. Prior to chemotherapy, 98 pts on the G Berne4, Sandoz-Wander Pharma Ltd Berne 5, Switzerland arm received G 3 mg IV and those on the G+D (219 pts) From February 1992 to April 1994, 734 patients in 45 centres were given or D (216 pts) arms, G 3 mg IV and D 10 mg IV. In all 2514 cycles of ILg.pisetron (TRO) for treatment of chemotherapy induced three arms, this was followed by G I mg PO at +6 and nausea and ~omiting (N&V). TRO was given as a single daily dose of 5 rag, +12 hours. On day 2-7, pts received either G I mg PO intravenously on day 1 of chemotherapy to all patients and per os (as a bid or G I mg PO bid + 8 mg PO bid, or D 8 mg PO bid. capsule) on days 2 to 6 (in 41% of the patients), in the evening preceding Pts completed a self report diary daily on which the day 1 and on days 2 to 5 (in 33% of the patients) or following an other number of emetic episodes were recorded. An intent to schedule in 26% of the patients. Control of N&V was defmed as follows: treat analysis on all eligible and evaluable pts was complete = no V and no N or only mild N; partial = < 4 V episodes and/or < performed. Baseline characteristics were similar for 4 h moderate N; failure = > 4 V episodes and/or > 4 h moderate N or severe the three groups of pts. We compared the results of N. The median number of TRO cycles per patient was 3 (min 1, max 27). the G arm to G+D and those of D to G+D. Over the seen 25% of the chemotherapy cycles (643 cycles in 222 patients) contained day period, the proportion of pts who had no emesis, cisplatin or dacarbazin. no rescue medication and no missing data was 11% for A complete control of N&V in the high emetogenic chemotherapy setting G and 37% for G+D (P (0,001). The D group had a 36% (containing cisplatin or daearbazin) was observed in 85% of the cycles on control of emesis, a difference of I~ with G+D (p= day 1 and in 72% to 85% on days 2 to 6. A failure of control was observed 0.85; 95% c] -8% to 11~). The relative success rate in 2% of cycles on day 1 and in 4% to 2% on days 2 to 6. In the moderate on these three arms was not significantly different emetogenic chemotherapy setting (non containing cisplatin or dacarbazin) a when missing data were considered as successes. We complete control of N&V was observed in 88% of the cycles on day 1 and in conclude that D improves the efficacy of G but that G 84% to 93% on days 2 to 6. A failure of control was observed in 2% of alone has little activity on day 2-7. In addition, G cycles on day 1 and in 2% to 1% on days 2 to 6, Results similar to these adds little to D as G+D is as efficacious as D on day latters were observed in the 90 cycles of the 27 pediatric pts. The subgroup 2-7. Therefore G should not be used on day 2-7 follo- of 94 pts responding poorly to previous antiemetic therapy showed a wing HDCP. complete control in 78% of the 316 actual cycles, a partial control in 17% and a failure in only 5%. In all settings, both the 84% complete and the 12% partial control rates observed in the 734 ftrst cycles were again observed or even improved in the subsequent 513 second, 369 third etc cycles. The overall subjective tolerability of TRO was good in 93.5% of the cycles ADDING 5 HT3 ANTAGONISTS (5 HT3) TO and moderate in 6%. No serious adverse event was observed. The most 25* DEXAMETHASONE (DEX) AFTER TWENTY frequent adverse events were constipation in 2.5% and headache in 2.3% of FOUR HOURS HAS A MINIMAL EFFECT IN the cycles. Out of 36 pts (1.4%) who discontinued TRO, only 6 (0.2%) PREVENTING DELAYED ONSET NAUSEA (N) discontinued because of adverse events (headache, loss of appetite, reaction AND VOMITING (V) IN PATIENTS (PTS) at the injection site, restlessness). RECEIVING MODERATELY EMETOGENIC In conclusion, despite the open design, this study clearly documents the high CHEMOTHERAPY (MEC). *WS Lofters, B Zee, for efficacy, the safety and the tolerance of TRO, administered once daily at the the Symptom Control Committee of the National dose of 5mg, for the treatment of N&V induced by chemotherapy. Cancer Institute of Canada Clinical Trials Group and Nordic Merrell Dow Research Canada, Queen's University, Kingston, Ontario, Canada K7L 3N6

As a component of a larger study 402 pts treated with DEX 8 mg IV and either 2.4 mg/kg dolasetron (DOL) or 32 mg ondansetron (OND) prior to 340

7* ORAL ONDANSETRON 8 MG BID IS AS patients experience emesis without antiemetic prophylaxis); EFFECTIVE AS 8 MG TID IN THE PREVENTION OF Category 2 (10 - 30%); Category 3 (30 - 60%); Category 4 NAUSEA AND VOMITING ASSOCIATED WITH (60 - 90%); Category 5 - (> 90% experience emesis). For CYCLOPHOSPHAMIDE-BASED CHEMOTHERAPY. combination regimens the following algorithm was *T Beck MD, M York MD, A Chang MD, developed: the emetogenic level is derived from the most R Navari MD, W Harvey MD, M Meshad MD, emetogenic agent in the combination. Agents in categories 1 L Kalman MD, T Dobbs MD. Mountain States and 2 do not change the emetogenicity of a given Tumor Institute, Boise, ID combination regimen. Combining two category 3 agents, two This multicenter, randomized, double-blind study evaluated the category 4 agents, or a category 3 and 4 agent will increase efficacy and safety of ondansetron (OND) 8 mg administered twice daily the emetogenicity of a given combination by one level. This compared with three times daily for 3 days in the prevention of nausea classification schema provides a framework for the and vomiting in 402 patients on cyclophosphamide (>500mg/m2)-based development of antiemetic treatment guidelines for common chemotherapy. The first dose of study drug was administered 30 rain chemotherapy regimens. prior to initiation of chemotherapy (cyclophosphamide and either doxorubicin >_40mg/m2 or methotrexate >30mg/m2). Efficacy data were statistically analyzed for patients completing the study period without major protocol violations (efficacy population; n=336); safety data were 29~ TESTING AN ACTIVE ALL-ORAL SINGLE DOSE COMBINATION ANTIEMETIC REGIMEN. analyzed for the intent-to-treat population (n=402). The results show that *RJGralla, CN Rittenberg, LA Lettow, MG the percentage of patients with no emetic episodes over the 3-day study Peralta, biD Cronin. period was 61% in the OND BID group compared with 58% in the OND Ochsner Cancer Institute TID group (n.s., Fisber's Exact test). Among patients with at least one New Orleans, Louisiana, USA emetic episode, the mean time to emesis was 14'17" in the OND BID group compared with 12'48" in the OND TID group (n.s., Wilcoxon Rank With single agent antiemetic activity when given orally or IV, both the 5-HT3 antiemetics and Sum test). Patients' daily appetite ratings and nausea scores were not corticosteroids are logical choices to be used in an significantly different between groups. Subset analyses on patients who all-oral combination regimen. To test this received only doxorubiein, only non-doxorubicin regimens, only high- hypothesis, we treated 61 patients receiving dose cyclophosphamide, or only low-dose cyclophosphamide did not cisplatin (DDP) with the following regimen: DEX 20mg reveal differences between the BID and TID groups with respect to PO PLUS granisetron lmg PO (with low dose DDP proportion of patients with no emetic episodes, mean time to emesis, 60mg/M2) or granisetron 1.5mg PO (with high dose DDP - i00 mg/M2). The antiemetics were given only at 30 appetite ratings, or nausea scores. Clinical laboratory and adverse event minutes before DDP. The liquid injectable form of profiles were also similar between groups. The most common potentially the antiemetics was used orally and mixed in 30 ml drug-related adverse event was headache, occurring in 22% of OND BID of water, producing a colorless, odorless, and patients and 30% ofOND TID patients. This study is the first Iarge-scaIe, nearly tasteless single dose. Patients were double-blind trial to demonstrate that OND 8 mg BID, a dosing regimen previously untreated or had no emesls with prior chemotherapy; male:female = 80%:20%; median age 66; that may enhance patient convenience and compliance, is as effective as high dose (HD) DDP = 51%. All patients also received OND TID in the prevention of nausea and vomiting associated with oral agents for delayed emesis (DE) with DEX plus cyclophosphamide-based chemotherapy. The BID dosing regimen may either a 5-HT3 antagonist or metoclopramide prove to be valuable for the increasing number of chemotherapy patients beginning at 16 hours after DDP. All patients were being treated on an outpatient basis. followed for 5 days with results given below for complete control of acute emesis (initial 24 hours), DE (the next 4 days), and Acute + DE (All 5 days): COMPLETE CONTROL OF: ACUTE EMESIS D__EE ACUTE + DE A PROPOSAL FOR CLASSIFYING HD DDP: 31 84% 65% 61% 28* LD DDP: 30 87% 80% 80% THE EMETOGENICITY OF CANCER BOTH : 61 85% 72% 70% CHEMOTHERAPY * P. J. Heskethl, T. Beck2, S.M. Grunberg3, Side effects were mild with headache in 23%. J. Hainsworth4, G. Harker5, M. Kris6, St. Potential cost savings are high with i) low pharmacy and nursing charges for an oral regimen, and 2) high Elizabeth's MED CTR, Boston, MA1, MNT efficacy with only one-half to one-third the ST Tumor INST, Boise, 1/)2, UVM CAN granisetron dose needed as generally given in most CTR, Burlington, VT3, Sarah Cannon CAN countries. We conclude: 1) this all oral, single dose regimen appears to be at least as effective as CTR, Nashville, TN4, VA MED CTR, Salt high-dose or multidose IV combinations (95% CI = 74% Lake City, UT5, MSKCC, N'Y, NY6, USA to 93%), with excellent side effect and economic profiles; 2) the delayed emesis regimen may contribute to control of both Acute and DE; and 3) At present, there is no widely accepted schema for classifying randomized comparison trials are warranted. the emetogenicity of chemotherapy. Existing classification systems do not consider important treatment related variables such as dose, rate and route of administration and do not SINGLE INTRAVENOUS BOLUS DOSE OF provide a framework for predicting the emetogenicity of 30* 5-HT 3- RECEPTOR ANTAGONISTS IN combination regimens. Our goal was to develop a consensus CHEMOTHERAPY INDUCED EMESIS. statement on a practical schema for classifying the * Bruno Massidda M.D., Maria Teresa lonta M_D., emetogenicity of cancer chemotherapy. Information on Antioco Scanu M.D., Maria Rcstituta Foddi M.D. emetogenicity was obtained through literature reviews as well Chair of Medical OneoloKy Cagliari University, Italy. as the clinical experience of the authors. The information base for the classification schema was derived from adult The weigh of the costs and benefits of the treatments is more and more cancer patients receiving common doses of chemotherapy under valuation. Even if the 5-HT3-r-antagonists offer an higher percentage administered by short intravenous infusion. Chemotherapy (with lower toxicity) of complete control in cisplatin-induced emesis than agents were divided into 5 categories: Category 1 (< 10% of conventional drugs, they arc more expensive. Since the 5-HT3-r-antagonists 341

are usually used also in non-cisplatin regimens in i.v. load dose at 1st day COR excretion are significantly related to poor control of CIE. Measurement and p.o. for at least 3 subsequent days, in order to optimize the dose and of COR excretion can add infomlation to an individual risk-profile for CIE. consequently the costs we started a study involving sixty naive breast Further studies are necessary to evaluate if COR excretion levels can help to cancer pts in age from 30 to 71 years, PS = 0-1 (median 0), candidate to identify those pts. who will benefit from combination anti-emetic therapy moderately emetogenic adjuvant or palliative FEC 75 or q 21 CMF or Mito including steroids. Furthermore, combination of COR values with other risk- C + MTX + MITOX or q 14 dose intense FEC or MMM (+G-CSF) or q 21 factors might help to create therapy strategies based on individual risk 120 mg/m2 Epirubicin. Pts were randomized to receive 15 m' before factors, which might help avoiding mmecessary and cost-intensive treatment. chemotherapy 8 mg i.v. Ondan~tron (ARM A; 2(1 pts) or 3 mg i.v. Granisetron (ARM B; 20 pts) or 5 mg i.v. Tropi~tron (ARM C; 20 pts) and no further ant(emetic therapy in the following days. Responses on 180 evaluable cycles are: VOMITING (%) NAUSEA (%) ACUTE DELAYED ACUTE DELAYED AN ANALYSISOF THE ONSET OF EMESIS INDUCED BY ARM A B C A B C ,A B {? A B , C 32* CYCLOPHOSPHAMIDE CONTAINING CHEMOTHERAPY IN PATIENTS RECEIVINGORAL GRANISETRON Grade 0 75 70 70 70 82 72 56 37 21) 50 35 27 Orade 1 23 19 9 28 12 12.3 28 28 35 28 33 37 Orade 2 2 9.3 9 2 2.6 7.7 15 26 32 17 30 33 M. Aapro (I,2&4) and *J-PTerrey (3) on behalf of the granisetron study group. Grade 3 0 1.7 12 0 3.4 8 1 9 13 5 2 3 1= H6pital Cantonal. CH-1211 Geneva, 2= Clinique de Genolier, CH-1272 Genoller, 3= SmithKline Beecham AG, CH-3174 Th6rishaus, & 4= g 0 = no votniting / nausea; g 1 = 1 episode / mild nausea; g 2 = 2-4 episode / European Institute of Oncology, IT-20141, Milano. moderate nausea; g 3 = > 4 episodes / severe nausea. The statistical analysis (Mann Whitney test, t Student, Anova) showed no Cyclophosphamide is widely used for the treatment of a variety of tumours and significant differences between the three drugs as regard the acute (A vs B p is thought to Contribute to delayed emesis. We performed a longitudinal analysis of the onset of emesis (vomiting with or without moderate to severe nausea) in 0.139; A vs C p 0.919; B vs C p 0.246) and delayed vomiting (A vs B p patients (pts) who received iv cyctophosphamide containing chemotherapy (CC) 0.312; A vs C p 0.804; B vs C p 0.268) while in the acute and delayed without cls or carboplatin. Data was extracted from a large multicentre, nausea Ondansetron seems superior to Granisetron (p 0.018 and p 0.104) multinational randomised double blind dose ranging study comprising 936 and Tropisetron (p 0.05; p 0.01) without difference between Granisetron and chemotherapy (C) naive pts designed to evaluated the antiemetic efficacy of the Tropisetron (p 0.113; p 0.130). The three drugs in i.v. single dose showed an selective 5HT3 antagonist granisetron. All pts were randomised to 1 of 4 oral granisetron doses; (0.5, 1, 2 or 4 mg bd for 7 days) as antiemetic therapy. high and similar activity in the control of vomiting both acute and delayed, Antiemetic efficacy data was collected for 7 dayspost C from 559 pts undergoing practically the same that we obtained employing them with load dose at day ivCC. 65% and 51% of all CC treated pts had no more than mild nausea at 1 and maintenance for 3-5 days (Ann. Oncol. 1994, 6, suppl. 8, 204). 24hrs and 7 clays respectively. No statistically significant differences (p>0.05, Considering, moreover, the not negligible percentage of failures of Chi-square test) between the CC groups or granisetron doses were detected in conventional drugs, the costs may be very little different from these latest. this population. The onset of emesis by day is tabulated below. Percentage (n) of pts who present with first symptoms of emesis. Day of study to first emesis. 0 1 2 3 4 5 6 Cyclophosphamide Dose. (n) 1'R ARE MEASUREMENTS OF PRE-THERAPEUTIC <600mg/m2 35 11 3 0.6 0.2 0 0.4 SEROTONIN AND CORTISOL EXCRETION (446) (158) (46) (12) (3) (1) (0) (2) PREDICTIVE FOR PLATIN-INDUCED EMESIS ? * A.du Bois t, W.Vach 2, U.WechseP 6~176 30 6 1 0 1 0 1 (67) (2O) (4) (1) (0) (1) (0) (1) 1 Dept.Gynecology St.Vincentius Khs Karlsruhe, 2 Zentrum fOr Datenanalyse University Freiburg, >T50mg/m2 43 11 0 0 4 2 0 3 Dept.Gynecology University Freiburg, GERMANY (46) (20) (5) (0) (0) (2) (1) (0) Pt~rpose: To evaluate if pre-chemotherapeutic parameters of serotonin (5-HT) 35 10 2 0.5 0.6 0.2 0.5 or cortisol (COR) metabolism could help to define a subgroup of patients Total (559) (198) (55) (13) (3) (4) (1) (3) with a high risk for carboplatin-induced emesis (CIE). Methods: The excretion of 5-hydroxyindoleacetic acid (5-HIAA, the main We conclude that the onset of 5HT3 refractory emesis following CC occurred metabolite of 5-HT), 5-HT, and COR were measured in urine samples within the first 24 hrs in 35% of these pts and waned over the proceeding 6 days. collected in the night before chemotherapy. 5-HIAA and 5-HT values were 4% or less of these pts presented with first symptoms after day 2. Further investigations are warranted to determine the role of different C agents in divided through creatinine values to correct for varying urine concentrations. delayed emesis. ht order to avoid bias from circadian rhythms COR excretion was quantified in a standard 12 h collection period from 8 p.m - 8 a.m. Emesis was recorded over dl-5. In a first analysis pts. with or without emesis were compared regarding their pre-therapeutic 5-HIAA, 5-HT, and COR levels. In a second analysis pts. with low, medium, and high values of 5-HIAA, 5-HT, and COR were compared with respect to whether they vomited or not. PATTERNS OF CYCLOPHOSPHAMIDE-INDUCED Results: 65 pts. receiving carboplatin > 300 mg/m 2 containing regimens 33 "k were included into the 5-HIAA/5-HT analysis. COR analysis was performed EMESIS REFRACTORY TO 5-HT3-ANTAGONISM *U. Cramer-Giraud t, A. du Bois t, W. Vach 2, in 28 pts. Ant(emetic therapy consisted of ondansetron (67%) or metoclopramide (33 %). In thg~ 5-HT group emesis occurred in 40% on dl-5, C. Thomssen3, M. Fiola 4. while 57% in the COR group showed emesis on dl-5. Neither 5-HIAA nor IDept. Gynaecology, St.-Vincentius Khs., Karlsruhe; 5-HT values were different in pts. with or without tIE. Furthermore, pts. 2Zentrum f/it Datenanalyse, Freiburg; 3Dept. Gynae- with low, medium, or high 5-HIAA or 5-HT values showed nn difference cology TU Mfinchen; 4Glaxo, Hamburg; GERMANY regarding CIE. Pts. with emesis had significantly lower COR values compared to pts. without CIE (median 83.6 /~g vs 136 /zg; p= 0.03). A Purpose: To evaluate the patterns of cyclophosphamide (CTX) - induced second analysis revealed a significant correlation of low COR values and CIE emesis refractory to 5-HTa-antagonism with ondansetron (OND). To des- (p= 0.04). Logistic regression including age as a variable confirmed this cribe the impact on patterns of emesis of epirubicine (EPI), carboplatin result (p= 0.02). Defining 110 #g COR/12 hrs. as cut-off value results in a (CBDCA), or both, when combined with CTX. sensitivity of 0.88, a specifity of 0.67, a positive predictive value of 0.78, a Methods: We analyse the patterns of emesis (frequency, severity, onset, negative predictive value of 0.8 for tIE in pts. with lower COR values. duration) in 402 pts enrolled into an open ant(emetic study with OND 8 mg Conclusion: Pre-therapeutic measurement of 5-HT metabolism failed to I.d.s dl-5. CTX dose was 500-1000 mg/m2. Only female pts were included. define a group of pts. with a high risk for CIE. Low levels of pre-therapeutic Mean age was 51-56 yrs and was well balanced between the CT regimens. 342

Results: CMF CC t CEC 2 EC FEC TWICE DAILY ORAL ONDANSETRON 35 EFFECTIVELY PREVENTS NAUSEA AND n 216 97 19 31 39 VOMITING ASSOCIATED WITH CYCLOPHOSPHAMIDE-DOXORUBICIN-B ASED vomiting dl-5 39% 45% 74% 61% 62% CHEMOTHERAPY. nausea dl-5 63% 52% 89% 77% 79% *J DiBenedetto MD, L Cubeddu MD, T Ryan MD, J Kish MD, D Sciortino MD, C Beall MD. vomiting dl 25% 21% 47% 52% 38% Oncology/Hematology Associates, Providence, RI

vomiting d2-5 28% 38% 58% 42% 49% Oral ondansetron 8 mg TID for up to 3 days is effective in the prevention onset (days) 4 1.49 1.81 1.50 1.21 1.37 of chemotherapy-induced nausea and vomiting. This multicenter, randomized, double-blind study evaluated the efficacy and safety of eND duration (days) 4 1.96 1.81 2.64 1.89 2.79 8 mg BID for three days compared with placebo in preventing nausea and vomiting in 81 patients on cyclophosphamide (>500mg/m2)-doxorubicin EE 3 dl-54 6.76 5.63 11.00 7.29 11.17 (...>40mg/m2)-based chemotherapy. The first dose of study drug was administered 30 min prior to initiation of chemotherapy. Patients ~CC: Carboplatin-CT) 2CEC: Carboplatin-EPI-CTX, 3numbersof emetic episodes received a rescue antiemetic if the investigator deemed it necessary or if 4means in pts who vomited al least once on dl-5 they experienced > 2 emetic episodes during the 3-day study period. Conclusion: Efficacy data were statistically analyzed for patients completing the study 39% pts experienced CMF induced emesis despite eND prophylaxis. The period without protocol violations (efficacy population; n=67); safety data combination with EPI leads to a higher frequency of emesis on dl-5. Onset were analyzed for the intent-to-treat population (n=81). The results show of emesis commenced earlier in EC/FEC (p<0.05). Duration of emesis is that the percentage of patients with no emetic episodes over the 3-day longer and emesis is more severe in the combination CT regimens. The ad- study period was 61% in the eND group compared with 6% in the dition of EPI changes patterns of CTX-induced emesis. To avoid bias the placebo group (p<0.001, Fisher's Exact test). Among patients with at impact on emesis of different cytostatics when combined with CTX should least one emetic episode, the mean time to emesis was 24'18" in the eND be taken into account for the design of future studies. group compared with 8'1" in the placebo group (p<0.001, Wilcoxon Rank Sum test). Seventy*eight percent of patients in the eND group compared with 29% of placebo patients completed the study without the need for "CONTROL'* OF HIGH-DOSE-CHEMOTHERAPY- rescue therapy. Clinical laboratory and adverse event profiles were 34* INDUCED EMESIS; ONE MORE REASON FOR similar between groups. The most common potentially drug-related CONTINUING ANTIEMETIC RESEARCH. adverse event was headache, occurring in 23% of eND patients and 22% *JA Lopez-Martin, M Martin, A Casado, Y Nieto, F Ayala, of placebo patients. This study is the first double-blind, placebo- JL AIonso, T Portugal, JV Alvarez, P Perez-Segura, E controlled trial to demonstrate that eND 8 mg BID, a dosing regimen that Diaz-Rubio. Servicio de Oncologia. Hospital Universitario San Carlos. 28040-MADRID. SPAIN. may enhance patient convenience and compliance, is effective in the prevention of nausea and vomiting associated with cyclophosphamide- Emesis is one of the most common acute toxicJties of high-dose chemotherapy (HDCT), doxorubicin-based chemotherapy. The BID dosing regimen may prove to and little is published about the efficacy of anti-5HT3 in its prophiMxis. O We describe the be valuable for the increasing number of chemotherapy patients being emetic pattern of 81 patients ipts) with breast cancer treated with HDCT at our institution treated on an outpatient basis. from 9/92 to 5/95. They were admitted on day -8 in order to begin with overhidration. HD CT consisted in ciclophosphamide 5 9/m 2, thio-tepa 500 ilqg/m 2, carboplatin 800-1600 mg/m2 and mitoxantrone 0-50 mg/m2, all fraetionated into five daily doses delivered as a 2 hours iv infusion through days -7 to -2. Peripheral blood stem cells were collected and cdopreserved with DMSO prior to HDCT and reinfunded on day 0. O Antiemetie regimens 36 IV DOLASETRON MESILATE IN THE consisted in: A) Dexametbasone (D) 20 rng iv qd and ondansetron (O) 8rag PREVENTION OF RADIOTHERAPY- iv q8h, from day -7 to -1. Addition of another antiemetic was considered if INDUCED NAUSEA AND VOMITING the patient had more than 2 vomits in 24 h. B) D+O, same doses, plus haJoperidot (Hi 1 mg q8h. 19 The evaluable period has been from day -7 to *P Bey, PM Wilkinson, N Claverie, et al. -1, because DMSO-induced emesis can occur on day 0, and it is a different Centre Alexis Vautrin, Vandoeuvre-Les- problem. As part of the daily work-up, we wrote down on every pt chart the Nancy, France; Christie Hospital, Manchester, number of vomiting events (VE), the maximum number of VE in 24 h (MVE), UK; MMD, Strasbourg, France. tl~e duration of VE (DYE), tile maximum intensity of nausea (MN) (grades 0- 3), the duration of nausea (DN) and the time to the 1st VE (TFV) and to the This double-blind, placebo-controlled, multicenter study 1st N (TFN). O We have prospectively assessed the emesis in 81 pts, all women, with a median (m) age of 46 years (range 26-60). 49 pts were assessed safety and efficacy of single IV doses of dolasetron treated with regimen A (D+O), including 11 who precised the addition of mesilate (DM) for the control of emesis caused by single high- other antiemetic, which was H in 8. Given that the latter one decreased the dose (>6 Gy) radiotherapy (RT) of the upper abdomen. Fifty subsequent MVE in more than 50% in 3/8 pts, the following 32 were treated cancer patients (stratified by naive or nonnaive to RT) received with regimen 13 (D+O+ti). In 10 of these pts H was withdrawn because of extrapiramidalism (6 pts within the first 48 hi. O Results: No significant placebo (PL), 0.3, 0.6, or 1.2 mg/kg DiM prior to RT and were differences between emetic control in both groups have been observed. In monitored for 24 hours. Antiemetic efficacy was assessed prima- the whole sample, the total number of VE per pt during the studied period, rily from time to first emetic episode (EE) and/or administration has been 10 (m) (range: 0-44). MVE has been 4 (m) (0-20) and the DVE has been 4 days (m) (0-7). MN has been 2 (m) (0-3) and Dig has been 4 days of rescue medication (RM) and secondarily from number of EE, (m) (0-7). TFV and TFN have both been 2 days (m) (0-=). In 23 pt we could patient and investigator assessment of nausea, and investigator's precisely evaluate the average TFV: 56 hours. Only 4 pts (4.9%) had MVE=0 assessment of efficacy. Treatment differences between DM and and MN

administration of RM (p=.006). Complete response (0 EE, no June 1993 to August 1994 we enrolled 25 consecutive pts with HIV-NHL in RM) did not differ significantly for total DM vs PL (54%, 91%, a prospective randomized study comparing granisetron (3 rag/day, prior to 71%, and 58% for PL, 0.3, 0.6, and 1.2 rng/kg, respectively, CT) and ondansetron (8 mg prior to CT, 4 and 8 hours post-CT) as follows: p=.217) but was significant at the 0.3 mg/kg dose (p=.050). No pts received one of the antiemetogenic drug at the odd cycles and the alterna- significant treatment differences were recorded for patient satis- tive drug at the even cycles. The aim of this study was to evaluate the antiemetogenic and antinausea efficacy of both drugs. The evaluation of this faction, self-assessment of nausea, or investigator assessment of efficacy was made with the strict cooperation of the nurses with a question- efficacy. Treatment-related adverse events were rare and mild to naire every 6 hours for 2 days after CT administration. All pts were admitted moderate in intensity. We conclude DM was effective and well- to the ward during this study. The majority of our pts were intravenous drug tolerated in the control of single, high-dose RT-induced emesis, users (IVDUs, 12/25) but at the time of CT they were not reporting the use of with a tendency toward superior efficacy in RT-nonnaive illecit drugs. All pts were treated with moderately emetogenic CT regimens in- patients. cluding cyclophosphamide, doxorubicin, vincristine, Neomycin, etoposide, mitoxantrone and prednimustine at the standard dosage. The median age of our pts was 35 years (range 25-79 years) and the total number of administered 37 OPEN LABEL IV DOLASETRON MESYLATE IN PEDIATRIC PATIENTS RECEIVING MODERATELY cycles was 70 (36 with ondansetron and 34 with granisetron). Twenty-one TO HIGHLY EMETOGENIC CHEMOTHERAPY: pts,who received at least 2 cycles of CT, were considered evaluable for this PHARMACOKINETICS, EFFICACY AND SAFETY. study. During CT no significant difference between the two groups was *J. M. Leclere t, M. Greenberg~, R. Lau 2, L. lngram 3, R. observed: 8 episodes of N-V with ondansetron (4 G1, 3 G2 and 1 G3 accor- Grant't, D. Howard~, L. Larivirre 6, M. Perrotta6, E. ding to WHO) and 7 episodes of N-V with granisetron (5G1 and 2 G2). The Dempsey6 overall incidence and nature of adverse events were similar in both groups. Hrpital Ste-Justine, Montrdal, Que, Canada; 2 Hospital Our data show that both ondansetron and granisetron are highly effective for Sick Children, Toronto, Ont, s Janeway Child Health Centre, St. John's, agents for prophylaxis of emesis in pts with HIV infection and tumors Nfld, 4 Alberta Children's Hospital, Calgary, Alta, 5. 6 Marion Men-ell Dow, s receiving moderately emetogenic CT regimens. Granisetron may be preferred Kansas City, Mo. USA and 6 Laval, Que., Canada. because it is administered in a single dose and it is less expensive. These aspects are very important in a population of pts such as ours (mainly IVDUs) Dolasetron mesylate (D) is a potent and selective 5HT 3 receptor antagonist with many economical and social problems. which has been shown in healthy male adult subjects to be rapidly and Study supported by AIRC and ISS grants. completely metabolized to MDL 74156 (M) which reaches a maximum concentration within 1.0 h after dosing and is eliminated slowly with a half- life of 6-10 h. (M) is responsible for the antiemetic action of (D). An open label dose escalating design was used to assess the PK, safety and efficacy of 0.6, 1.2, 1.8 and 2.4 mg/kg doses of (D) administered by I.V. infusion 30 minutes prior to start of moderately to highly emetogenic chemotherapy in 46 EFFICACY OF ONDANSETRON AND pediatric patients. (M) was quantitated using validated HPLC of serial 39 METOCLOPRAMIDE ( WITH plasma samples. All adverse events, use of rescue therapy, and emetic DEXAMETHASONE ) : IN THE PREVENTION OF episodes were recorded in a 24 h diary. A 12 lead ECG was recorded before CARBOPLATIN-INDUCED EMESIS. dosing, 1 and 24 h post (D). Of the 46 patients, 63% were male, median age 10.7 yr, median Karnofsky status 88.5%, and 87.0% were non-naive. Peak * A du Bois, H Andersson, M Lahousen. H concentrations of (M) were observed 0.41 to 0.61 h (tin,x) post (D) infusion. Kitchener, T Pinter, V Capstick, CJ McKenna, Mean plasma maximum concentrations were 135.5 to 738.7 mg/ml for the * St Vincentius-Krankenhauser, Karlsmhe, Germany. 0.6 to 2.4 mg/kg doses of(D) respectively. The mean plasma half-life (hn) in this pediatric cancer population was approximately 5 h for all doses as The management of ovarian cancer involves the administration of aggressive compared to 7 h in healthy male adult subjects. Mean apparent clearance chemotherapy agents such as CAP and single agent carboplatin. The use of (CI,~) was 1.5-2.0 times greater than in healthy adults. Complete response ondansetron given either alone or in combination with dexamethasone in the rates were 10%, 25%, 66.7% and 33.3% in the 0.6, 1.2, 1.8 and 2.4 mg/kg prevention of carboplatin-induced emesis has not been extensively studied. groups respectively. The most frequent adverse events were headache (13%) This study was therefore undertaken to evaluate the efficacy of ondansetron and tiredness (13%). This incidence was similar to that in adult patients. plus dexamethasone and metoclopramide plus dexamethasone in the There were no serious adverse events. Treatment-emergent increases in PR, prevention of carboplatin-induced emesis. QRS and QT c intervals were seen but all were asymptomatic and not This study was an international, double-blind, parallel-group study conducted clinically significant. in 189 patients suffering from ovarian cancer. Patients were randomised to Conelusion: The PK profile of (M) in children is similar to adults although recieve either intravenous ondansetron 8mg plus intravenous dexamethasone the ttn is decreased (33%) and the Cl~,p is increased (2.0 fold). Based on 20mg on day 1, followed by oral ondansetmn 8rag twice a day on days 2-3, or these data 1.8 mg/kg appears to be the most effective dose for further study. intravenous metoclopramide 60rag plus intravenous dexamethasone 20mg on Doses up to 2.4 mg/kg of IV (D) were safe in this pediatric population. day 1, followed by oral metoclopramide 20mg three time a day on days 2-3. Results showed the ondansetron regimen to be significantly superior to the meloclopramide regimen on day 1 and days I-3. 8 RANDOMIZED COMPARISON OF GRANISETRON VS ONDANSETRON INPATIENTS (PTS) WITH HIV- ] Emesis (<2 emetic episodes) Emesis (0 emetic episodes) RELATED NON-HODGKIN'S LYMPHOMA (HIV- Regimen Day 1 Days 1-3 Day 1 Days 1-3 NHL) RECEIVING MODERATELY EMETOGENIC OND 97%* 87%* 93%* 74%* CHEMOTHERAPY (CT) REGIMENS. MET 74% 66% 66% 48% * M. Spina, M. Valentini, P. Fedcle, D. Bemardi, G. * p<0.001 Nasti,C. Simonelli, S. Santarossa, S. Sandri, R. Talzunini Nausea (V none or mild) Nausea (none) and U. Tirelli. Division of Medical Oncology and AIDS. C.R.O., Aviano - Italy. Regimen Day 1 Days 1-3 Day 1 Days 1-3 OND 96%* 80%* 91%* 56%* There are no data published in the literature regarding granisetron and ondan- MET 72% 65% 57% 37% setron in patients with HIV infection receiving CT for malignant tumors. From * p

Fewer patients from the ondansetron regimen (13%) reported adverse events before each RT. Subsequent pts (3 per group) were to receive compared with the metoclopramide regimen (21%). The combination of doses of 20, 30, 40, or 50 mg before each RT; administration of ondansetron plus dexamethasone is a highly effective, well tolerated treatment higher doses was contingent upon the tolerability of the smaller in the prevention of carboplatin-induced emesis and nausea, and is doses. Efficacy was assessed using complete response (CR: 0 significantly superior to metoclopramide plus dexamethasone. emetic episodes [EEl and no rescue medication [RM]), CR + major response (CMR: 0 to 2 EE and no RM), time to first EE/ RM, and nausea severity. A significant linear trend with increas- OPEN LABEL ORAL DOLASETRON MESYLATE IN 40 ing dose was detected in percent ofpts with CR: 62%, 85%, PEDIATRIC PATIENTS RECEIVING MODERATELY TO HIGHLY EMETOGENIC CHEMOTHERAPY: 73%, 100% and 92% in the 10, 20, 30, 40, and 50 mg groups, PHARMACOKINETICS, EFFICACY AND SAFETY. respectively, (p=.002). Linear trend was also statistically signifi- *R. Yanofsky 1, A. Pyesmany 2, S. Pritchard 3, J.M. cant for CMR rates (p=.0002) with best results in the 40 and 50 Leclerc*, C.B. PrattS, D. BakerS, D. Howard 6, L. mg groups. Four pts received rescue medication; all were in the Larivi~re 7, M. Perrotta 7, E. Dempsey 7 10 mg dose group. There were no significant differences among Manitoba Cancer Foundation, Winnipeg, Man., Canada, 2 I.W.K. Hospital, treatments for patient's nausea or time to first EE. DM was well Halifax, N.S.; 3 B.C. Children's Hospital, Vancouver, B.C.; 4 L'H6pital Ste- Justine, Montr6al, Que.; s St Jude Children's Research Hospital, Memphis tolerated across dose groups. Most frequently reported adverse Tenn.; 6. 7 Marion Men'ell Dew, 6 Kansas City, Me.; and 7 Laval, Que., events were dry mouth, fever, and headache (4% for each). In Canada all, DM was effective and well tolerated in the prevention of high Dolasetron mesylate (D) is a potent and selective 5HT 3 receptor antagonist dose RT-induced emesis, with best results at the 40 and 50 mg which has been shown in healthy male subjects to be metabolized to MDL doses. 74156 (M) which reaches a maximum concentration within 1.0 h after dosing and is eliminated with a half-life (tla) of 6-10 h. (M) is responsible for the antiemetic action of (D). The PK, efficacy and safety of (D) in pediatric EFFECTIVE ANTI-EMETIC THERAPY IMPROVES patients undergoing moderately to highly emetogenic chemotherapy was 42 QUALITY OF LIFE (QOL) AFTER MODERATELY assessed. Doses of 0.6, 1.2, and 1.8 mg/kg (D) were administered orally 30 EMETOGENIC CHEMOTHERAPY (MEC). *JL min. prior to chemotherapy in an open label dose escalating design. (M) was Pater z, B Zee I, WS Lofters T, D Osoba T, D. Warr t, M quantitated using validated HPLC of serial plasma samples. All adverse Palmer~, C Chin2, E Dempsey 2. 1National Cancer events, use of rescue therapy, and emetic episodes were recorded in a 24 h Institute of Canada Clinical Trials Group and 2Nordic diary. A 12 lead ECG was recorded pre-, 1 and 24 h post-(D). Of the 32 Merrell Dew Research Canada, Queen's University, patients studied, 47% were male, median age 10.4 yr, median Kamofsky Kingston, Ontario Canada K7L 3N6 status 90%, and 100% were non-naive. Mean plasma maximum concentrations of(M) observed within 1 h (t~,) post (D) administration were It has long been claimed that failure to control nausea and vomiting (NV) 54.7 to 264.0 mg/ml for 0.6 to 1.8 mg/kg of (D) respectively. The t~a in this after chemotherapy adversely affects quality of life, but there is little if any pediatric population ranged from 5.2 to 6.2 h-as compared to 8 h in.healthy empirie evidence demonstrating that superior anti-emetic control is reflected male adults. Mean apparent clearance (Clapp) was 2.5 times greater than in in better QOL as measured by a validated instrument. In a study comparing adults. Complete response rates were 33.3%, 30.8% and 50% in the 0.6, 1.2 dolasetron (dol) to ondansetron (end) +/- dexamethasone (dex) 696 patients and 1.8 mg/kg groups respectively. The most frequent adverse event was were randomized in a factorial design to receive one of four regimens (IV dol headache (19%). The incidence of adverse events was similar to that in adult +/- IV dex or IV end +/- IV dex) immediately prior to MEC. NV were patients. There were no serious adverse events. Two patients experienced measured by patient diaries. QOL was assessed with the EORTC QLQ seizure post (D) while receiving ifosfomide chemotherapy. Treatment- (230+3 administered prior to chemotherapy and on day 4 or 8 after emergent increases in ECG intervals were seen but all were asymptomatic chemotherapy. Overall the administration ofdex markedly improved NV both and not clinically significant. IV administration has been similarly studied. acutely and over the seven days post MEC while the differences between dol Conclusion: The tlr2 of (M) is decreased (25%) and the Clapp is increased and end were moderate acutely and disappeared over the post 24 hour period. (2.5 fold) in children compared to adults. Based on these data 1.8 mg/kg of These differences were reflected in QOL assessments. When changes in QOL oral (D) appears to be safe and the most effective dose. The rapid clearance scores from baseline were compared in pts receiving or not receiving dex, may support further study of a slightly higher oral dose. significant differences in favour of dex were found for: global QOL, physical and social function and in the symptoms fatigue, pain, NV, appetite loss, constipation and diarrhea. In the dol to end comparison the only significant QOL difference was in the symptom constipation. We conclude that anti- 4"1 ANTIEMETIC EFFICACY & SAFETY OF IV emetic therapy which results in substantial improvement in NV control also DOLASETRON IN CANCER PATIENTS produces detectable benefits with respect to broader aspects of QOL. AFTER HIGH-DOSE RADIOTHERAPY. *PM Wilkinson, P Bey, JP Gerard, JF Bosset, et al. Christie Hospital, Manchester, U.K.; 43 CORRECTED QT INTERVAL VALUATION Centre Alexis Vautrin, Vandoeuvre-Les-Nancy, IN 5-HYDROXYTRYPTAMINE - RECEPTOR- France; Centre Hospitalier, Pierre Benite, ANTAGONISTS TREATED CANCER PATIENTS. * Maria Teresa Ionta M.D., Paolo Piredda M.D., France; Hopital Jean Minjoz, Besancon, Antioco Scanu M.D., l) Alessandro Bina M.D., France. t)Patrizio Bina M.D., t)Maurizio Bina M.D., t)Anna Maria Loy M.D., Bruno Massidda M.D. This open-label, multicenter trial assessed the antiemetic efficacy Medical Oncology University, 1) Cardiology, and safety of a range of single doses of IV dolasetron mesilate Cancer Hospital Cagliari. Italy. (DM) in patients (pts) with cancer requiring high-dose radio- 5-HT3-receptors antagonists are effectively used in preventing the therapy (RT: including upper abdomen, mid-plane dose (4-10 chemotherapy-induced emesis without relevant clinical side-effects. Gy/day). In all, 76 pts from 8 centers completed the trial. The Since Ondansetron has a detectable binding at non 5-HT 3 sites (5- first 3 pts at each center received 10 mg IV DM 15 minutes HTlb.lc) and Tropisetron at 5-HT4 and 5-HT2c-uptake sites and 5-HT 345

receptors are found in the human cardiac atria, an arthythrnogenic 5 ONDANSETRONAND DOMPERIDON IN PATIENTS potential of these drugs as a dose-dependent prolongation of the QTc RECEtVtNG 3 COURSES OF FEC FOR BREAST CA. interval cannot be excluded.Aim of our study was to evaluate the QT P1nar Saip,M.D.~Haluk Onat~M.D.,Sevil E. interval on the surface ECG expressed as the rate corrected maximum tnan~,M.D.,Erkan Topuz,M.D. interval according to Bazett (QTr = QT/~,,/E~-R) before (To) and after at tstanbul Univ. Institute of Oncolo~y~ least 3 cycles of therapy (TI-T2-T3). In 121 cancer pts (97 females; PS tstanbul-Turkey 0-1; from 31 to 72 years), treated with >60mg/m2 cisplatin-including (45 pts) or not chemotherapies plus Ondansetron (16 nag i.v. day 1 + The efficacy of po. ondansetron(OD) and domperidon 16 mg p.o. on day 2-5; 46 pts) or Granisetron (3 nag i.v. day 1; 41 pts) (DO) in the prevention of emesis during 3 subsequent or Tropisetron (5 mg i.v. day l + 5 nag p.o. on day 2-5; 34 pts). courses was studied in 3] patients(pts) with breast Results are: cancer receiving fluorouracil, epirubicin and cyclo- T n T! T 2 I',] phosphamide(FEC). Pts were given OD 8mg. rid. on day ONDA 0.394 0.389 0.397 0.380 1, and DO 20mg. rid. on days 2-3. Global control(GC: (p 0.980) (p 0.816) (p 0.597) (p 0.643) 0-2 episodes of vomiting, none/mild nausea, no/mild GRAN! 0.398 0.407 0.407 0.402 change in nutritional habits) for acute vomiting, (p 0.836) (p 0.622) (p 0.650) (p 0.464) nausea and nutrition were 78~ 55 and 55% respectively. TROPI 0.391 0385 0.394 0.39.8 GC for delayed vomiting, nausea and nutrition by QTc values above the maximum normal range, but not clearly worst day analysis were 74, 58 and 58 % respectively. patological, were found at T O in 4.9% of cases equally prorated among The cumulative efficacy of OD decreased from 78%(CI the three arms and in 9.9% during the cycles (4.9% ONDA, 2.5% 0.92-0.63) to 48%(CI 0.66-0.29), and of DO from 74% GRANI, 2.5% TROPI; p = n.s.). In conclusion, the sligth increase of (CI 0.90-0.59) to 53%(CI 0.7]-0.35) during 3 courses. the QTc that we found sporadically are bereft of clinical impact and not Progressive loss of efficacy was most pronounced in surely due to 5-HT3-r-antaginists since it may be also correlated with nausea. OD and DO were found to be effective and well- the antiblastics (as doxorubicin) and / or hyperydratation in cisplatin theraphy. tolerated in the prevention of acute and delayed vomiting, but not so successful in controlling nausea and disruption of nutrition. Antiemetic efficacy should be determined during multiple courses of chemo- therapy with evaluation of quality of life measures NASALLY ADMINISTERED such as nutrition in addition to episodes of nausea 44 METOCLOPRAMIDE (MCP) FOR THE and vomiting. PREVENTION OF CISPLATINUM (CDDP) INDUCED DELAYED EMESIS. 6 EMESIS DUE TO HIGH DOSE CYCLOPHOSPHAMIDE (HDCTX) AND MELPHALAN (HDL-PAM): AN EPIDEMIOLOGICAL STUDY t~ C.Locatellt, A.D'Antona, A.Pessi, G.Luporini *LUciD Patoia, M.D., Antonella Giglietti, M.D., Anna Stivaktaki, M.D., and Medical Oncology Dept. S.Carlo Borromeo Hospital Milan, Italy. Albano eel Favem, M.D. Institute of Internal Medicine and Oncology Sciences, University of Perugia. 06100 PERUGIA, ITALY Delayed emesis is a distressPal complication of CDDP chemotherapy OQ..BJECTIVES : In a previous epidemiolegicat study we observed a very high mid it affects most patients treated with this drug. Dexametazon incidence of vomiting (V) due to HDCTX (95%) and HDL-PAM (83%) despite (DXM) and MCP are considered the drugs of choice for treating a standard antiemetic prophylaxis with steroids, ondansetron (Ond) and Haloperidol (Halo). delayed emesis; in this clinical situation they are administered V due to HDCTX eacured, in mean, after 10 hrs from the first bolus and was prevalent in the first 3 days intramuscelarly and orally. Tweh,e palients (pts) affected with (d). After HDL-PAM emeais was more severe, mostly occurred after the first 3 d and lasted up to 20 d. In consideration of the emesis characteristics we decided to modify the antiemetic regimen by advanced solid tumors, median age 62, male/female ratio 1/I I, treated increasing and fraotionating the total dose of drugs and extending the duration of prophylaxis. Nausea (N) with CDDP-based chemotherapy, in single or multiple days, receiving and Vcharacteristics ware assessed in 35 consecutive patients (pts) (8 males and 27 females, 17 treated with HDCTX and 18 with HDL-PAM) suffering from solid tumors or hemalotogic DXM + Ondansetron to prevent the acute phase of emesis, were malignancies to evaluate the emesis control obtained with this modified regimen. Preitminary results treated for I single course with MCP nasal spray formlflation at the are presented. METHODS: HDCTX schedule: five doses of 1.4 g/sqm (total dose 7 g/sqm) over I hour i.v. infusion, every 3 beurs (hrs). HDL-PAM schedule: 200 mg/mq in 3 divided doses i.v. bolus every following doses: MCP 20 mg (--2"puff') 8 and 16 hours after CDDP 2 hrs in 9 pts. 7 pts received 140 mglsqm L-PAM in combination with t600 rng/sqm ARA-C, 800 adanhfistrafioJt hi the day of chemofllerapy hi pts submitted to shxgle mg/sqm VP-16 and 30Q mg/sqm carmustine and 2 pts busuftan 16 mg/kg x 3 days plus L-PAM 140 mg/sqm.. Antiemetic emchvtaxis for HDCTX ets: DAY 1; Daxametason (Dex) 4 mg iv five times/day (total day CDDP, or in the last day of CDDP for the ffactionated regimens; dose 20 rag) before each HDCTX bolus or Methylprednisotone (Mtp) 250 mg before the first HDCTX in the following 5 days MCP was given every 8 hours; in 6 pts MCP bolus; Ond: 8 mg iv before the 1", 3 ~ 4", 5" HDCTX bolus (total dose 32 rag). DAYS 2-3: Dex 8 m9 iv every 12 hrs (total dose 16 mgld) or Mtp125-250 mg/d + Ond 8 mg iv eveq/12 hrs (total dose16 rag/d). was associated to DXM 8 mg x 2 irn for 2 days and 4 mg x 2 im for Antiemotir croehylaxis for HD-LPAM pts: DAYS 1-3:17 pts received: Dex 8 mg iv every 12 hrs (total dose another day. During the acute phase of the study emesis was absent 16 rag/d) + Ond 6 mg iv every 12 hrs (total dose 16 mgld) + Halo 1 mg us every 12 hrs (total dose 2 rag). 1 pt received only Dax +Ond with the above mentioned schedule. DAY >3 : pts received Dex 8 mg (n. of emeiic episode - EE - 0) in 9 pts, in tile 5 subsequent days after every 12 hrs (total dose 16 mg/d) until the beginning of neutropenia (neutmphil count < 1000/ul) and Ond administra~on of CDDP (delayed phase) 3 pts had no EE throughout 8 mg every 12 hrs until emesis completely disappeared for at least 2 consecutive days. Incidence, severity, onset and duration of N and V were evaluated once a day until emesis completely all the 6 days following CDDP administration (2 treated with nasal disappeared. MCP alone and 1 with nasal MCP + DXM ira). The an~iemetic RESULTS: The preliminary results can be summarized as follows: treatment was devoid of major sidc-cffccts. "l'hc s)raptoms judged as PTS with V: OVERALL DAY 1 DAY 2-3 DAY 4-t0 DAY 1%20 CTX LPAM CTX LPAM CTX LPAM CTX LPAM CTX LPAM possibly related to treatment with MCP were somnolence (3pts), 12117 16/18 8/17 2/18 12/17 10/18 6/17 15118 -- 6/18 diarrhoea (3pts); in every case these side effects were mild and (71) (88) (47) (11) (70) (56) (29) (83) - (33) V reversible; t lot experienced a single episode of mild epistaxis during EPISODES: 7 12 5 4 3 3 4 9 -- 4 the second day of trea~nent with MCP nasal spray, but it was not MEAN- 1-20 1-43 %15 1-7 1-tl 1-10 1-13 1-32 -- 1-7 RANGE judged a controindication to continue the endonasal administration of MCP. We think that this new formulation of MCP deserves further "New"PTS ...... 8 2 4 8 0 5 0 with V: clinical evaluation in pts undergoing cytostatic chemotherapy CTX LPAM CTX LPAM especially in those clinical situations in which MCP is actually Overall Overall Complete 5/17 2/t8 Major 3/17 1/18 considered the drug of choice. protection : (29) (11) protection: (18) (6) 346

At day 1, the mean onset of V from starting chemotherapy was: HDCTX 11 hi's, HDL-PAM 10 hrs. The Reduction of nausea and vomiting after chemotherapy of last day of V was 5 in the HDCTX and 12 in the HDL-PAM group. 49 CONCLUSIONS: In comparison with our previous study the use of fractionated antiernetic regimen patients with breast and ovarian cancer by a novel combi- seems to be useful In reducing only the incidence of V in the HDCTX treated pts, due to a betler control in nation of antiemetics. the ftrst 3 d after treatment, A possible reduction in the duration of V was also found. No other differences in HDCTX-related emesis characteristics were observed with respect to our previous study. No * Amain Conrad, M.D., Harald Meden, M.D., differences in the characteristics of emesis due to HDL-PAM were observed; the incidence is still very Oliver Meil3ner, M.D., Walther Kuhn, M.D. high, V mostly ocourrod after the first 3 d and lasted longer than following HDCTX as we described in our previous study. Despite the use of an antiemetic regimen tailored on the characteristics of emesis, N and Department of Obstetrics and Gynecology V due to HDCTX and to HDL-PAM still remain a retevant unresolved clinical problem. Furiher study with Georg-August -University of GOttingen different combination an.I/or schedule are needed. GOttingen, Germany iMPACT OF TUMOUR BURDEN AND AGE ON 47 DELAYED EMESIS The quality of life of patients treated with cytostatics is influenced by the *Timo J Hursti, Dr Med Sc, Elisabeth AvalI-Lundqvist, control of side effects, such as nausea and vomiting. Ondansetron is a highly M.D., Sussanne B6rjeson, R.N., Mats Fredrikson, effective antiemetic drug for patients undergoing chemotherapy with cisplatin. Ph.D., CarI-Johan FOrst, M.D., Gunnar Steineck, Its potency in other chemotherapy regimes, such as carboplatin for ovarian M.D., Curt Peterson, M.D. cancer or CMF for breast cancer, has not yet been elucidated. Dept of Clin Neuroscience, Dept of Oncology, Karolinska Institute, Stockholm, Sweden. The current investigation examined the efficacy of two different antiemetic treatments in patients with breast and ovarian cancer. Nausea and vomiting after The mechanisms of acute chemotherapy induced nausea and each cycle of chemotherapy were evaluated with a questionnaire. vomiting have been extensively studied during the recent years. Concerning delayed emesis our knowledge is much more Ovariari cancer (n=35): The basis of this investigation were 68 chemotherapy inconclusive. The aim of this study was to investigate how age and cycles with carboplatin (350 mg/m2) and cyclophosphamide (600 rag/m2). residual tumour burden after cytoreductive surgery are related to the Monotherapy with ondansetron (3x8 rag) was compared to a combination of occurrence of acute and delayed nausea and vomiting. One hundred ondansetron and bromazepam. Nausea could be controlled in 65% of and one ovarian cancer patients receiving their first chemotherapy chemothrapy cycles by the combination of ondansetron and bromazepam. In course including cisplatin (50 mg/m2), doxorubicin and melphalan, contrast, monotherapy with ondansetron was effective only in 38% of participated in the study. The antiemetic treatment consisted of chemotherapy cycles. Vomiting could be completely suppressed in 93% of ondansetron 8 mg x 3 iv and 20 mg dexamethason or placebo. After chemotherapy cycles by the combination of ondansetron and bromazepam, in chemotherapy at[ patients received ondansetron 8 mg x 3 po for 5 81% of cycles by the sole medication of ondansetron. days. Tumour burden was classified in two categories according to the diameter of the greatest residual tumour: < 2 cm and > 2 cm. Self- reports of nausea and vomiting were obtained for fourteen days Breast cancer (n=18): 36 cycles of chemotherapy with cyclophosphamide (600 starting from the chemotherapy day. Patients with tumour burden < 2 rag/m=), MTX (40 mg/m2) and 5-FU (600 mg/m2) were evaluated. The cm were free from nausea in higher degree on the chemotherapy day. combined antiemetic therapy with alizapride, dexamethasone and bromazepam Also, concerning emetic episodes, complete response was more was compared to a monotherapy with ondansetron. A combined therapy led to a frequent in these patients especially days 3 - 7. The occurrence of complete suppression of nausea in 78% on the first day of therapy and in 83% nausea was higher in patients > 55 years compared to those < 55 on the second day of therapy. In contrast, ondansetron was effective in 58% on years during the second week after the chemotherapy. Generally, the first day and in 43% on the next day. A complete control of vomiting was there was an interaction effect showing that the aggravating effect reached using the alizapride combination in 83% on the day of therapy and in associated with larger residual tumour burden was more evident in 92% on the following day. Compared with the monotherapy with ondansetron, a older patients and vice versa. complete suppression of vomiting could be achieved in 97% on the day of therapy and in 83% on the day after chemotherapy, 48 FACTORS AND PARAMETERS AFFECTING Our concept improves the quality of life of patients with breast and ovarian THE OUTCOME OF ANTIEMETIC THERAPIES cancer. IN PATIENTS RECEIVING CISPLATIN-BASED CHEMOTHERAPY. A RETROSPECTIVE STUDY. * Tsavaris N, Kallergis G, Mylonakis N, Karvounis N, Bendenidis C, lakovidis V, Bacoyiannis C, Kosmidis P. 0 CARBOPLATINUM-INDUCED EMESIS 2rid Department of Medicine and Department of Psychiatry, Metaxa REFRACTORY TO ONDANSETRON Memorial Hospital, Piraeus, Greece. * M. Glaubitz 1 l A. du Bois, In 301 patients undergoing cisplatin-based cytotoxic chemotherapy U. Cramer-Giraud, C. Thomssen we evaluated different factors that are thought to affect the outcome for the German Multicenter of antiemetic medications with metoclopramide (1-2 m/kg). The ~ndansetron Study Group factors which were studied were: previous chemotherapy regimens Dep. of Obst. and Gynecology (215 patients), anxiety (168 patients; Hamilton's scale), family Hannover Medical School compliance, and senous personal problems (87 patients; modified Hannover, Germany scale of Holms & Rahe), weight loss (25 patients; WHO scale), performance status (243 patients; WHO scale 80-100, 58 patients; In order to study the pattern of WHO scale <80). The number of emetic episodes with or without carboplatinum-induced emesis refractory to gastric content as well as the duration of nausea was evaluated by 5-HT3-antagonism , 184 female and 32 male the attending medical personnel. After performing, multivariate patients (mean age 55 yrs) receiving a analysis of the data there is a trend in affecting emes~s parameters single day carboplatinum-based chemotherapy for the following factors: severity and duration of nausea by (~250mg/m ~) enrolled in an open multicenter performance status (P<0.094), vomiting without gastric contents by trial. Antiemetic prophylaxis consisted of anxiety (P<0.087), and vomiting with gastric contents by previous ondansetron 8 mg IV prior to chemotherapy chemotherapy (P<0.089). followed by 8 mg x 2 PO on day 1 and 8 mg Conclusion: In the present study, it appers that the most important x 3 PO on days 2 to 5. Nausea and vomiting factors related to cisplatin-induced emesis are: anxiety, previous (N/V) were recorded by a patient's diary on chemotherapy, and performance status. days 1 to 5. 347

Acute emesis occurred in 22% (47/216) and combination with methylprednisoleme iMP) 4 mg/kg x I ac~inistered with nausea in 75% (155/216) of patients on day highly emetogenic chemotherapy in pediatric oneology patients treated at I. Within the five day observation period, home. Sixteen patients received a total of 66 chemotherapy courses at least one emetic episode was recorded in (cisplatin + doxorubicin, or ifosfamide + etopaside, or doxorubicin + 44% (96/216) of patients. The median number cyclophosphamide) through a home care chemotherapy delivery program. of emetic episodes for this patients was Antiemetic outcomes were assessed following completion of chemotherapy four. On average, the N/V period began 40 with a previously validated nausea/vomiting (N/V) survey. Patients hours after chemotherapy with a mean and/or parents (for patients < 9 yr) indicated the number of vomiting or duration of 48 hours. The risk for N/V on retching episodes (VE) and rated nausea severity (NSEV), vomiting days 2 to 5 was higher in patients already severity (VSEV), and daily activity interference (DAI) on a 4 point suffering from emesis on day 1 (relative scale (O=none, 1=mild, 2=moderate, 3=severe). Results indicated the risk 2.44). following mean + S.D. scores for all patients: NSEV=O.88• Carboplatinum-induced emesis refractory to VSEV=0.74~O.93, DAI=0.67• and VE=I.5~2.8. Successful control of 5-HT3-antagonism showed a monophasic N/V was defined a priori as NSEV, VSEV, and DAI scores of 0-I. prolonged pattern, which might be triggered Successful N/V control was achieved in the following percent of courses: by a serotonine-independent mechanism. NSEV=84.~k, VSEV=78.8% and DAI=78.8% The average home care agency charge for this antiemetic regimen was 113 U.S. dollars (USD) per day of PILOT STUDY OF THE ANTIEMETIC chemotherapy, which added approximately 15% to the mean chemotherapy 51 EFFICACY OF DOLASETRON IN regimen charge. The antiemetic charge per successfully treated patient LEUKAEMIA PATIENTS RECEIVING was 133 USD (NSEV), 143 USD (VSEV), and 143 USD (DAI). OND plus MP TOTAL BODY IRRADIATION (TBI) AND allowed for successful treatment of pediatric patients in the home CHEMOTHERAPY BEFORE BONE-MAR setting who were receiving highly emetogenic chemotherapy. Prior to the availability of OND, hospitalization was required for children receiving ROW TRANSPLANTATION. *AA Fauser, highly ematogenic chemotherapy due to risk of antiemetic toxicity (e.g., M.D., Medical Director, Klinik ftir extrapyramidat reactions). The feasibility of a home care program in H~imatologie/Onkologie und pediatrics has resulted in dramatic monetary savings for payers Knochenmarktransplantation, Idar-Oberstein, (approximately $2254 per chemotherapy treatment), with relatively small Germany additional charges for antiemetics. This charge per success for this antiemetic regimen is a potential benchmark for comparisons with other This 5-day open-label, pilot trial assessed the antiemetic safety antiemetic regimens and other treatment centers. and efficacy of oral dolasetron mesilate (DM) in 20 acute This study was supported in part by a grant from Glaxo Research leukaemia patients (pts). Pts received 3 days of fractionated TBI Institute. (2 Gy/twice a day) followed by 2 days of IV chemotherapy (CT) with cyclophosphamide 60 mg/kg/day. DM doses of 50, 100, or 150 mg (a 200 mg dose was added for CT) were administered i 3 RESPONSE TO TROPtSETRON IN ADULTS AND hour before each radiotherapy (RT: 2 x day) and CT (I x day). CHILDREN PREVIOUSLY UNDER POOR ANTIEMETIC Antiemetic efficacy was assessed using complete response (CR: CONTROL USING ONDANSETRON *Y. Benoi'~1 , V. Cocquyt 2, S. Van Belle 2, L. Ritter 3 0 vomiting/retching), CR + major response (CMR: 0-2 vomiting/ IDptmt Ped Hemet.-Oncology, UZ Ghent; 2Dptmt Oncology, retching episodes), and physician assessment of nausea level UZ Ghent; 31nt Inst for Drug Devel, Brussels, Belgium. (none, mild, moderate, severe). After 3 days of R T, CR was Antagonists of the 5-HT3 receptor have become standard of care in the recorded in (3/5) 40%, (1/1) 100%, and (8/14) 57% of pts at 50, prevention of nausea and vomiting following the administration of 100, or 150 mg DM, respectively. CMR on days 1,2, and 3 was emetogenic chemotherapy. Studies in which the currently available drugs reported in 86%, 93%, and 93% of pts receiving 150 mg DM. of this class were compared as parallel groups are rare. Even more sparse On day 3 of RT, physician assessment of nausea indicated _< are results obtained when a patient is switched to a different 5-HT3 mild nausea in (3/5) 60%, (1/1) 100%, and (11/14) 79% of pts in antagonist following poor control in a previous course. We report here the results of an exploratory subgroup analysis of the the 50, 100, or 150 groups, respectively. For CT, CMR was Belgian open-label studies in 131 children [1] and 869 adults [2] treated observed on day 4 in 7/10 (70%) and on day 4 in 4/10 (40%) with 5 mg tropisetron (NOVABAN/ NAVOBAN) once daily (0.2 mg/kg pts receiving 200 mg DM. For physician assessment, rild with a maximum of 5 mg for the younger children) in the prevention of nausea was observed in 42% of pts on day 4 and 39% on day 5 chemotherapy-induced emesis. The following three criteria were used in the definition of the subgroups. First, the reason reported for switching of CT. DM was well tolerated with headache (30%) the most to tropisetron had to be poor antiemetic control in the preceding cycle of commonly reported adverse event. In conclusion, the antiemetic chemotherapy. Second, the previously used antiemetic agent had to be efficacy and safety evidenced in this pilot trial by DM 50, 100, ondansetron (27 children and 45 adults were thus identified). Third, the 150, and 200 mg in RT-induced emesis and the lesser efficacy chemotherapy had to be identical for the preceding cycle and the first shown in controlling CT-induced emesis (post RT) merit further course in which tropisetron was used. Cases where corticosteroids were study in randomized controlled trials. added to ondansetron or tropisetron were also excluded from the analysis. Sixteen children and 22 adults (38 patients overatl) fitted all three criteria and were analysed for their antiemetic control in the first course in which EVALUATIO~ OF THE CHARGES AND EFFICACY OF AN ONDANSETRON tropisetron was used. Complete antiemetic control (no nausea and no 52 PLUS METHYLPREDNISOLONE ANTIEMETIC REGIMEN IN PEDIATRIC vomiting) was obtained for day 1 in 7 out of the 16 children and 11 out ONCOLOGY PATIENTS TREATED AT HOME. *M.T. Ho[dsworth, + of the 22 adults (47 % overall). Two children and 5 adults (18 % overall) § Pharm.~., D.W. Ralsch , Ph.D., C.M. Chavez , BSN, M.H. remained completely free of nausea and vomiting for the five day # observation period. Duncan , M.D., T.V. Parasuraman, , Ph.D., College of + , These results need to be interpreted with caution given that they concern Pharmacy and Division of Pediatric Oncotogy , an exploratory analysis. Our data suggest that following an incomplete University of New Mexico, and Glaxo#, Inc. response to one 5-HT3 antagonist for the prevention of chemotherapy- induced nausea and vomiting, it may be worthwhile to consider the use of The purpose of this study was to evaluate the charges and efficacy another 5-HT3 antagonist. In the choice of a 5-HT3 antagonist, the associated with the use of ondansetron (OND) 0.15 mg/kg Q4h x 3 in simple administration schedule of tropisetron offers an additional 348

advantage. Given the uncontrolled nature of these studies it remains The efficacy of MPN and OND + DEX over time at subsequent impossible to provide accurate estimates of the probability of success in courses was also evaluated : 60% of pts at their 12th CMF course and this situation. For this reason, these data should not be used to compare 85% of pts at their 6th course mantained adequate antiemetic the efficacy the two 5-HT3 antagonists. Controlled studies are required protection (less than 5 emetic episodes) Adverse effects were to confirm our observations. generally mild and consisted of headache (10 pts with MPN, 3 pts with 1. Y. Benoit et al. ASCO 1994 Meeting, Abstract 14"77. OND, 6 pts with OND+DEX), facial flush (36 pts with MPN, 10 pts with 2. H, Bleiberg et al. Drugs 43 (Suppl 3): 27-32, 1992 (interim analysis). OND+DEX) and constipation (2 pts with QND, 6 pts with OND+DEX) In conclusion both the combination ondansetron+ steroids and the same agents used alone provide safe and effective prophylaxis in outpatients treated with moderately emetogenic chemotherapy, 54 THE HIGH EFFICACY OF NAVOBAN Pharmacoeconomic evaluation of the different options will be (TROPISETRON) IN PATIENTS RECEIVING presented. CYTOSTATIC CHEMOTHERAPY (CT). *Lichinitser M., Kirsanov A. Department of combined therapy 56 ASSESSMENT OF THE ANTIMETRIC EFFI- N.N.Blokhin Cancer Research Center CACY OF ONDASTRON IN CANCER CHIL- DREN BASED ON 4-YEARS EXPERIENCE. Moscow, Russia Roma Rokicka-Milewska M.D.,Ph.D., El• Rola-Kurtz M.D.,Artur Navoban (N.) was used in 61 patients (pts) receiving Gadomski M.D. CT (28 testicular cancer, 14 ovarium cancer, 12 Dept.of Paediatric Haematology and Oncology Medical Academy, lung cancer, 7 breast cancer) to prevent nausea Warsaw,Poland. and vomiting. Ondasetron /Zofran-Glaxo/ was applied as an The pts have not received any CT before. In all of antiemetric drug in 199 children treated for cases cisplatin (DDP at 120 mg/m 2) was used with cancer in the course of 650 chemotherapy cy- another cytostatic drugs. N. was given at 5 mg i.v. cles in the years 1991-1995.The first group included children treated with cisplatyna over 15 min prior to CT on day 1. 42 pts (68,8 %) and ifosfamid who were given Ondasetron pre- of 61 have had complete antiemetic effect in the ventively three times daily at a dose of 5mg /m2 every 8 h. The second group of children first 24 hours. Partial effect (1 - 4 episode of who were treated with less emetogenic regi- vomiting) in 16 (26,3 %) pts. Without effect in 3 ments were administered Ondasetron at a sin- (4,9 %) pts. On tne next 2 - 6 days 78 pts have gle dose. The third group received Ondasetron therapeutically once up to three times due had complete antiemetic effect. 64 -100 % of pts to the vomiting which appeared despite the have had complete effect of nausea on the 1 - 6 administration of other antiemetic drugs. Co- od results obtained after the application of days. In the repeat courses (up to 5 courses) the Ondasetron have been observed in all cases antiemetic effect was similar. and were similar in all groups. Complete lack These results show that N. has considerable of nausea and vomiting or occasional vomiti- ng /WHO degree 0-I/ was determined in the fi antiemetic effect. It has changed the notion of pts rst in 66.4%,in the second in 69%,and in the and physicians about side effects of moderne CT. third group in 66.7% of children. In the rema ining children occasional vomiting has been observed /WHO degree 2/.Tolerance of the dr- CONTROL OF MODERATELY EMETOGENIC ug was good.The efficacy of Ondasetron pro- 55 CHEMOTHERAPY INDUCED EMEStS:STEROIDS ved to be far more better than of all the an AND/OR 5HT3-RECEPTOR ANTAGONISTS? tiemetic drugs applied so far. *S.Chiara, MD, E.Campora, MD, R.Rosso, MD; Dept. Medical Oncology I, Istituto Nazionale Ricerca Cancro, Genova, Italy CLONAZEPAM IN TIlE TREATMENT OF 57 ANTICIPATORY NAUESEA / VOMITING In an effort to identify an effective, safe and economic schedule for INDUCED BY CYTOTOXIC THERAPY prophylaxis of emesis in cancer patients (pts) receiving moderately F. Mart6nyiI and M.V. Dank2 emetogenic chemotherapy on outpatient basis, the authors anaIized Scmmelwcis University School of Medicine, results of their consecutive trials conducted from 1987 to 1994. One Departments of Psychiatry~ and Radiology:,Budapest, hundred-fiftyseven breast cancer pts treated with CMF Hungary (cyclophosphamide+ methotrexate+ fluorouracil) or CEF (CF+epidoxorubicin) regimens on 1-day q, 21, received one of the One of the most distressing side effects of chemotherapy are the nausea following antiemetic treatment: 1) methylprednisolone (MPN) 40 mg and vomiting that some patients may suffered prior to their or 125 mg tds (Am J Clin Onco11987); 2) ondansetron (OND) 8 mg tds (Anticancer Res 1991); 3) OND 8 mg tds+ dexamethasone (DEX) 20 chemotherapy infusions. This anticipatory nausea and vomiting has been mg (Am J Clin Oncol ~t994). Complete protection (=0 emetic conccptionalised as result of classical conditioning processes. According episodes) from acute nausea and vomiting were as follows: the learning theory association is formed between nauseaHomiting Nausea Emesis (unconditioned stimulus) suffered after drug infusion (unconditioned MPN 43% 71% stimulus) and differont stimuli associated with the environment in which OND 68% 90% chemotherapy is administred (conditioned stimulus). Visual, olfactory, OND+DEX 38% 74% acustical, taste stimuli associated with chemotherapy , even cognitive 349

stimuli, such as the thought of chemotherapy have bccn found to elicitc ~ SIDE EFFECTS OF CONDITIONING REGIMENS nausea / vomiting in 20-50% of paticnts. Some psychologicalfactors, PRIOR TO BONE MARROW TRANSPLANTATION. especially anxicty, distress and dcprcssion arc associated with thc *P. Feyer, 0. Titlbach, F. Kamprad, dcvclopmcnt of anticipatorynauscaA, omiting. Anticipatorynausea has M. Kubel, A. Walter, V. Budach. proven resistantto treatment by differentantiemctic drugs: such as Dept. Radiotherapy, Medical School, halopcridol, mctoclopramide and 5HT3 antagonists.Lorazcpam and Charit6, Berlin, Dept. Radiotherapy and alprazolamscems to be cffcctiveas anti-anticipatoryemetic drugs. Dept. Hematologie, University Leipzig, Simillar to lorazcpamand alprazloamclonazepam, an otherhigh potential Germany. bcnzodiazcpinc scorns to be effectivein the prevcntion of anticipatory Conditioning regimens in preparing bone marrow trans- nausea and vomiting. plantation (BMT) represent an aggressive radio-chemo- The prevalenceof anticipatorynausea/vomiting was 14.8% within a therapy in order to achieve a complete tumor cell mixed, mostlybreast cancer, colon and rectum cancer patientpopulation kill immunsuppression and bone marrow ablation. in a one year period . Patientsverc treated by CEF, CMF, EIP, Gastrointestinal reactions (GIR) are the most common ADM+VCR and VIP combinationtotally in 274 cycles. Patientstrcatcd by acute side effects associated with high dose chemo- CMF suffered mostlyfrom anticipatrynansea/vomiting. therapy and total body irradiation (TBI) concerning Introductionof porcvntiver administration( I-2 mg p.o., 3 up to 80 % of patients. The resulting nausea and hours piror to the cytotoxictherapy) significantly rcduccd thc prevalence emesis are extremely distressing for the patient. of anticipatorynausea/vomiting : 5.2 %. The pateints were treated by different cmctogeulc cytotoxic drug combinations: CEF, CMF, EIP, We investigated 300 8MT-patients and compared single MMM, and with novantrone,ifosfamidc and ADM in monotherapy, all (STBI n=105) and fractionated (FTBI n=60) as well as together in 210 cylostaticcycles. The occurcnce of anticipatory busulfan (BU n=135) conditioning regarding to the nausea/vomiting correlated with the cmetogenic potential of the drug acute side affects especially frequency and combinations. possibilities of influencing GIR. The conditioning regimens were different in the frequency and severity of GIR. There is a determined dose dependency of vomiting during TBI (borderline dose between 2.0 to 4.0 Gy). The time interval between OUR EXPERIENCE, WITH IMPROVING QUALITY the fractions influence the incidence of GIR (shorter 58 OF ANTIEMETIC THERAPY interval) - and conventional antiemetics in 34 % but *M. WAGNEROVA, O. FROLO, I. ANORASINA, more effectively by 5-HT3 antagonists in 60 %. In BU- P. OUBINSKY, J. KLIMO conditioning GIR were not of importance. The STBI has Oeoartmerlt of Radiotherapy and Onco]ogy been replaced by FTBI in order to reduce toxicity. UNIVERSITY HOSPITAl_ !_.PASTEUR Reversible early reactions could not be reduced by 041 90 KOSICE, SI_OVAK REPUBLIC FTBI. As a result of replacing STBI by FTBI or BU and the use of more effective supportive therapy there was a decrease in severe complications. The cancer chemotherapy is almost always accompanied with urldersirable effects. The irltensity and relevan- cy of this complication depends on the type of cyto- statics, on dose intensity, on individual sensitivi- ty arid also on the quality of supportive therapy. Nausea and vomiting are among the most disturbirl.g side-effects of arltitumor chemotherapy. We aimed at improving antiemetic therapy (AT) for patients re- ~ OUR EXPERIENCE ON HIGH-DOSE CYSPLATIN ceivirlg chemotherapy. Still after introducing 5-HT 3 vv antagonists nausea ard vomiting constitute a ma.~or INDUCED NAUSEA AND VOMITING (N&V) therapeutic problem, fhcee staudar'disod AI ['ooimcns *L.Curreli, M.D., A. I~ianchi, M.D., and G.Mantovani, M.D. wet2 worked out. For each course of chemotherapy the patients were selected to one of the regimens by a Department of Medical Oncology, University of Cagliari, via S.Giorgio N. 12, 09124 Cagliari score of prognostic factors related to age, type of chemotherapy, anxiety and previous emesis problems. In spite of recent progresses, a significant minority of patients (pts) continues to have suboptimal A starldardised registration form was filled in daily antiemetic control. We reviewed our data about pts receiving HD CDDP with the aim to for five days by each patients to register episodes evaluate the efficacy of various antiemetic sel'tedules in the profilaxis of acute (A) and delayed (B) N&V induced by highly cmetogenic chemotherapy (30-100 mg/sqm of CDDP on day 1), titus of vomiting and degree of nausea orl a four level enabling a step ladder approach to be formulated based upon basal general conditions of pts scale. Authors analysed 594 courses of chemotherapy and/or previous response to other sntiemetie coverages. Bokh a series ofpts evaluable for acute with antiemetic therapy irl i34 patients . Arltiemetio N&V and a seres ofptsevahtable for delayed N&V wereobtained. As foracute N&V 212 p~s were evaltmb[e (200 M,12 F; mean age 58.4 years,range 31-78; 195 wi~ head and neck cancer therapy was succesful] trl 78% versus 75% versus 69% (HNC): 7 ,St I/, 49 St 1i'1, 139 St IV; 5 with lung ~ncer St IV; 8 with c:mphageal cancer:.4 St 111, in three different regimens. These results were ba- 4 St IV; I with mesotelioma St IV; 2 wid~ melanoma St IV; 1 with gastric cancer St lI. Pts sis for systemic improvements efforts which seemed received following antlemetic coverage for acute N&V: IA) granisetron (GILA)(3 mg i.v.), 2A) to increase the success rates. In our experience we ondansetron (OND) (24 mg i.v.) or 3A) tropisetron (-fRO) (5 mg i.v.) who were all giveaa at a single dose prior to administration of CDD~ 4A) one of above.stated 5.HT3-RA plus D (8 mg find quality of antiemetic therapy to be an useful i,v. prior to administration of 5-HTg-RA mad aRer 12 h on day 1); 5A) like 4A plus doxepin tool in improving orl individual and group levels. (Do) 75 mg every 12h and sulpiride (-qu) 50 mg every gh, since one day before chemotherapy starting. As for delayed N&V 111 pts Were evaluable (108 M, 3 F; mean age 56.7 years,range 31-78; 99 with HNc: 4 St II, 13 St III, g2 St IV; 3 with lung cancer St IV; 7 with esoplmgenl cancer:. 3 St lit, 4 St IV; 1 with melanoma St IV; I with gastric cancer St II. Pts received following antiemetic coverage for delayed N&V: IB) GILA. 2 mg on d2-d3, I nag d4-dS; 2B) OND 16 mg d2-d3, gmg d4- d5 or 3B) TRO 5 mg d2-ds, all orally administered; 4B) one of above.stated 5-HT3-RA plus D (g mg i.m. every 12 hX 5B) M 20 mg orally every 6 h; 6B) like 513 pins D (gmg i.m. every 12 h); 7B) like 4B phls Do 75 mg every 1211 and Su 50 mg every gh. All pts receiving treatments 5A) 7B) experienced a failure (F) or minor respoose (MiR) during previous cbemotberapy eyelcm.g22 chernotheralw cycles for acute and ,t68 for delayed na'uscu and vomiting were evahtated. Results were as follows: 350

sEandard dc:,ses (5 mg iv day I and ii~o days 22~ 11o (7~.o) ~7 ~15.9) Ii {4.7) 206 i~5 (7S.2) ]6 (17,5) 5 {2.4) i0 { 4.9) 3A 228 i~4 (67.S) ~9 (17,i) 21 (9.2) i~ (~.~) d~ys J.--2 i\.' .:~d-td .% ~TY~] po da~/'.-:5 3-5) t.tr"~d@~< 4A 130 ~18 (90.S) 7 (S.4) 3 {2.3) 2 (1.5) 5A 2S 21 (84.0) 4 (16.0) 0 (0.0) o (o.o) c~metc)g(!,-,nic: c:hem(]ther..=_q]y. ~.riclt:.dinq ,z(Jmb.~.na- pe~ayed ~&v ~..~,.(~:}F'l ~,:)"~: CiEplat.ir", 40 mg/m =~ days i to 3 ,and iS ~0 21 (4~.01 20 (40.0) ~ (10.0) ( ~.o} 28 111 g0 (sl.l) Id (14.4) S (4.S) ( o.ol Vep:J.side 150 ,ng/m = days 1-2. The first gro- 3B ~I 5= (ST,1) ~I (23.1) 12 (13.2) (~.~) up in(:].L, ded 27 pakients (67 courses)~ the 4S 44 4~ (S7.7} 1 (~o~) 0 (0.0) (o.o) 58 ZO S (4S.O} ~ (30.0) ~ (S.O) (lO.O) 2? "~ group ,::ctns:.Lsted c:~f J_6 patier-~Ls (29 co .... ~B 134 ii] (84.3) 16 (i~.0) ] (=,2) (i.s) L.trSE~"~5) ], bahc) were s (-c?r!$EeF'F~iPl(~] the 7B IS 14 (77.~) 4 (22.2) 0 (0.0) (o.o) cler"~er'a], parameter's> ( ].oc-~]. :i.~.::,l,::k(:]r= ai-:d type Accordint to our r~ulis and on the ground era r ratio reich a gradiml approach could Of '~.l,t~'lOP' ~ 77~ts s ~7~ (7;;}l J, icI ~ ~31--eseFice c-tl-ld Elra ..... be suggested to have an opiinml r of acute N&V: ONDIGRA/TRO-(F/MiR)-->S-IPF3- de of intrac:raniaI h)'iT3~f"tefiSJ.(.Df3 ) , Evz:).].tJa12.i .... RA+D-.(F/Ivli~->S-HT3-RA+D+Do+Su and folIowinll gradual approach to have sn 0pthna[ (::)n c~'f the ~::rfficiE~ney was performed every 24 coni~l of delayed NIV: M+D-.(F,q~iR).-->5-HT3+O-(FfMIR)--->5-HT3-RA+D+Do+Su I]ot.~rs ~t:)r- 5 days using the fo].lowing crite- Tr~olment 5-HT3-R.A+D+Do+Sa co.ld be snlgesi~I si,cr first chcmolherapy cycle ns ria,~ "cemp].ete" effect - the absence of n,.=.,- antlemctlc coverage [or pls both having more compromise gr condition~ or signs or high i_H75eL~ ~.~I'HJ vofl'iit~-ir]{]~!~ "partial"- episc~des of ~ucle emotional dis~'ess(deprassion>a.xir mid oilierexpre~ions or psychologicaldistress). VOmittiFIg 1-4 tTmes nr'ld of nausea for less thar'J 5 hour's, "absence" - 5 and more episo .... des of vomitting and nausea for more than 5 hours. Studying ar'~tJemetic ~_~nd aritir~ausea RANDOMIZED, DOUBLE-BLIND CROSS-OVER ef'fic:iei-~c:y in the .1. "~ and 2 ~'d grot.lps~ the 61 TRIAL OF THE ANTIEMETIC EFFECT AND co, replete effect ~.~as reg:i'ster'ed in ~',i]. the TOLERABILITY OF GRANISETRON PLUS patients on the 1 "t day; or'~ ?.he 2 ''d day - "7"7.8%, 6'7.4% .9.f'ld ~:]}'7.'.57,], ~'7.5"/,, respect, ivlv; PLACEBO (GRA) VERSUS GRA PLUS PRED- c~n t.he 2'..~~ day-69.7%, 6'7% and 87.5%:,81.25%; NISOLONE (PRE) IN PATIENTS (PTS) tin the 4 +~.h dav -- 96.4",/. ~ 87.87 arqd J,.C)C)",s 87.5"s; on the 5 th day --" 1OC)%, 98.2% arqcl RECEIVING CISPLATIN-BASED CHEMO- 100%, I0C)%. The lowest effect is rioted irl THERAPY (CT). ctnitdren of 1-3 years of age in the 1.-~t group and of 4-7 years of age in the 2 ~d c] r-c:xJ p. *J Handberg ~, V Wessel 1, L Larsen ~, J Herrstedt z, HH HansenL So, the well-e>'pressed antiemetic ac...... Departments of Oncology, The National University Hospital, tivity of navoban is est.ablished both under star~dard and "low" doses in children~ reci- Copenhagen ~ and Herlev ~, Denmark. eved highly emetegeni,:: c:heme'Eherapy for the bra i rt t uffic) F'S. Design: From January 1992 to November 1994 90 CT-naive pts were randomized to receive i.v. GRA 3 mg plus additional GRA 3 mg for a a total of ti.d. followed by 3 mg i.v. for 2-3 days or GRA (same schedule) plus PRE 50 mg daily orally for a 63 USE OF GRANULOCYTE-COLONYSTIMULATING maximum of three days.At the subsequent cycle of CT, pts were FACTOR (G-CSF) IN SOLID TUMOR (ST) crossed over to the alternative antiemetic treatment. 22 pts CHEMOTHERAPY (CMT): PROPOSED received single-day cisplatin-based (~ 50 mg/m ~) CT plus SCHEDULE OF LIMITED ADMINISTRATION. * Tsavaris N, Kosmas C, Papalambrou Ch, Unardaki G, cyclophosphamide or methotrexate. 68 pts received 3-days frac- Konstantopoulos K, Vayiopoulos G, Loukopoulos D. tionated CT with carboplatin day 1, cisplatin (~ 50 mg/m ~) days 2- Department of Medicine, Laikon General Hospital, 3 and ifosfamide days 1-3. University of Athens School of Medicine, Athens, Results: The median age (range) of the pts was 55 (25-73) years Greece. and 93% of the pts was women. 65 pts (72%) completed both cycles. CR (defined as no emetic episodes and no worse than Hematopoietic growth factors administered to patients undergoing mild nausea) 0-24 h after the first dose of cisplatin was obtained cytotoxic chemotherapy (CMT) for solid tumors (ST) have resulted in in 33% receiving GRA and in 53% receiving GRA plus PRE substantial reduction of hematologic toxicity. The aim of the present (p<0.01), study was to investigate whether the administration of G-CSF can be limited in patients with ST undergoing conventional CT, and therefore In the 68 pts who received 3-days fractionated CT the CR (days patient's discomfort, costs, and long-term sequelae be reduced. 52 1-3) was 9% with GRA and 9% with the combination (n.s.). patients underwent CMT every 21 days: 14 received FAC (5-FU 500 51 pts (57%) expressed a preference for one of the two treat- mg/m2-Adriamycin 50 mg/m 2-Cyclophosphamide 500 mg/m2) for breast ments, 27 pts (30%) favouring the combination and 24 (27%) cancer, 16 Carboplatin 350 mg/m2 monotherapy for ovarian cancer, 22 GRA alone (n.s.). Toxicity was minimal with no significant Carboplatin 300 mg/m2 dayl/Etoposide 100 mg/m2 days 1-3 for lung differences between treatment groups. cancer. CMT cycles were administered on the planned day provided the Conclusions: This study confirms 1) that prednisolone improves absolute neutrophil count (ANC)>2000/pl and platelet count the antiemetic effect of granisetron in the treatment of acute (0-24 (PLC)>100000//.11. The number of days required to administer G-CSF for h) cisplatin-induced emesis and 2) the very high emetogenicity of each patient individually was defined by the ANC on the day of the fractionated cisplatin CT. expected nadir ANC=1500-2000/,uI: 1, ANC=1(D0-1500/pI: 2, ANC=500- f000/pl: 3, <500:4 ampules (1 ampule = 300pg/day. G-CSF administration was discontinued when ANC>3000/pl and the next 2 ANT I El*lET I C EFF- I C I E:I,.ICY C]F: D ]: F: FIL:F;~EN ! chemotherapy cycle was administered 2 days after the last G-CSF dose. OE]SES QF NAV[]I~?.AN IIq (]77-tIL.[)REN Wt ]H None of our patients required hospitalization for febrile neutropenia (FN). MALI GNANT {[iRA I N T'UMORS. (3. G. J e ] o t ! d I-:: ct ,, a, t:::' hl]) ,, A. F ,, IB o t..t t:: h h y ,: The mean delay of planned chemotherapy cycles due to neutropenia was F' h I]), t'1[), El. t.s. I:: h o i cx::! c, v., A ,, G ,. 7::' r:{ 4:..,/k e ,, 2..2 days/cycle and the mean dose of G-CSF was 1.46 ampules/cycle. l::' !q[) ~ i~1., [+I , [)CJLI. b roy i r] ,, Conclusion: Limited administration of G-CSF, after taking into account C?ep~rtr-r~e~t: o f libr-s~:ir-~ [umor 1:Te~:]eT~.i

G-CSF (FILGASTRIM) ALLOWS THE i~1~ COADMINISTRATION OF GRANULOCYTE 64 ADMINISTRATION OF COMBINED COLONY-STIMULATING FACTOR WITH PACLITAXEL (P) AND EPIRUBICIN (E) WITH A METHOTREXATE, VlNBLASTINE, EPIRUBICIN HIGH DOSE INTENSITY IN PATIENTS WITH ANDCISPLATIN FOR THE TREATMENT OF ADVANCED AND METASTATIC BREAST CANCER : A PHASE l-ll CLINICAL TRIAL UROTHELIAL CANCER *F.Ries, C.Duhem, S.Rauh, M.Dicato *Mikio Igaw& M.D., Shinji Urakami, M.D.,Hiroki Department of Hematology-Oncology, Centre Shirakawa, M.D., Hireaki Shiina, M.D., Tomoyuki Hospitalier de Luxembourg, L - 1210 Ishibe, M.D. LUXEMBOURG Department of Urology Shimane Medical University In an ongoing phase I-II study, we combine a fixed dose of E Izumo, Shimane, Japan (100 mg/m2/w) with escalating doses of P (at planned levels of 135, 150, 165 rag/m2/2 w, 3 hours infusion) followed by G-CSF at 5 mg/kg/d s.c. The toxicity of combination chemotherapy is significant, with the d2-dlo in patients with advanced or metastatic breast cancer. At the most prominent side effect being myelosuppression. To reduce the dose level P 135 rag/m2, 6 patients have been included (age range 49- toxicity, we used a recombinant human granulocyte colony- 65 years), 32 treatment courses are evaluable (range 4-6 per patient). stimulating factor (rhG-CSF). A total et 52 patients were enrolled in A major toxic event occured in the first patient during the first course this study. The sites of tumor involvement included the urinary (neutropenic fever and grade 3 mucositis). This toxic event made the bladder in 24 patients, the renal pelvis in 5, the ureter in 4, lymph inclusion of 6 patients necessary, at dose level 1. No major toxic event occured in the 5 subsequent patients. Dose-intensity per week of 72 nodes in 11, bone in 4, the lung in 1, and miscellaneous sites in 4 mg/m2/w for P and 48 mg/m2/w for E (projected : 75 and 50 patients. The chemotherapy was given in 21 -day cycles as follows: respectively) was achieved. 30 mg/m 2 methotrexate was given intravenously on day 1, and The study is ongoing at dose level 2 with P : 150 mg/m2. 6 patients approximately 24 h later, 3 mg/m 2 vinblastine, 30 mg/m ~ epirubicin, have been included (age range 44-63 years) and 19 courses are and 70 rag/m2 cisplatin were given intravenously. The rhG-CSF (2 cvaluahle without a major toxic event. #g/kg per day) was injected subcutaneously on days 3 - 16 of each We conclude that G-CSF allows a high-dose intensity of both P and E. cycle. All patients received full doses of the antineoplastic agents Effectiveness of this association at various dose levels of P and the on time according to the protocol design. The response rates were maximal tolerated dose remain to be determined. 61% for primarysites, 55% for lymph nodes, 0 for bone, and 67% for miscellaneous sites. Of 42 patients evaluated, 5 (1.2%) achieved a 65 CHOP-MEVP SEQUENTIAL THERAPY complete response and 20 (48%) achieved a partial response, for an overall response rate of 60%. Of the 42 patients, 27 (64%) are WITH G-CSF SUPPORT FOR alive, and the median duration of survival is 14 months. The mean ADVANCED AGGRESSIVE LYMPHOMA nadir white blood count was more than 5,600 cells/mm 3. The *Toshiyuki Takagi, M.D., Chikara Sakai, M.D., incidence of mucositis in the total toxic symptoms was low. There was no cardiac toxicity or drug-related death. These results indicate Kyoya Kumagai, M.D. that the present combination chemotherapy with coadministration of Hematology-Chemotherapy Div., rhG-CSF is an effective and safe regimen for the treatment of Chiba Cancer Center Hospital, urothetiat cancer. Chiba 260, Japan CHOP-MEVP sequential therapy was scheduled as follows: HAEMATOP'OETIC GROWTH FACTORS AS ADJUNCTS 67 TO CONCURRENT CHEMO-RADIOTHERAPY IN HEAD ADM 45 mg/M 2, CPM 650 mg/M 2, VCR 2 rag/body on AND NECK TUMOURS day 1 and PSL 60 mg/M 2 on day 1- 5 (CHOP) ; mitoxantrone * Jens BOntzel M.D., Klaus K(Jttner, M.D. Division of ENd" 10 mg/M 2 (iv), vindesine 3 mg/M 2 (iv), on day 8, etoposide Kiinikum SuhlfTh(Jringen D 98527 SUN, Germany 140 mg/M 2 (iv) and PSL 60 mg/M 2 (po)on day 8-10 (MEVP); rG-CSF 2 /zg/kg (sc) on day 12-20. The therapy Myelotoxicity and mueositis are two of the most frequent side effects associated with was repeated every 21 days. Twenty patients were treated: chemo-radiotherapy comprising earboplatin and 5-fiuorouracil which is often 15 pts. with D large/mix, 3 Burkitt's and 2 ATL; 2 pts. implemented in the treatment of head and neck cancer. Because myelotoxicity can be overcome by administering haematopeetic growth factors we report here on our with stage 1I bulky mass, 7 stage ]]I, 11 stage IV. CR was experiences with a large group of 104 patients (69 men and 15 woman) who achieved in 17 (85.0%)of 20 pts. Overall survival and underwent such chemo-radiotherapy and who received growth factors to alleviate neutropenia and anaemia which had caused the combined therapy regimen to be relapse-free survival rate at 2 years were 48.8% and interrupted. With granulcyte colony stimulating factor (G-CSF) (filgrastim, n=75, standard dose 300 pg per day, administered subcutanously for 7 days), a significant 40.3%, respectively. Toxicity (>WHO Grade 3) : leucopenia increase in leucocyte concentrations with increased granulopoesis was observed in in 19 pts., thrombocytopenia in 12, anemia in 11, fever in the differential blood count within one day following commencement of treatment. With gra n ulocyte-macrophage eolonystimulating factor (G M-CSF)(molgramomostim, 16. Infection was documented in 4 pts. : septicemia in 2, n=20~ standard dose 300 gg per day, administered subcutanously for 7 days) a less C. difficile colitis in 1 and gingivitis in 1. There were significant increase in leucocyte concentrations was observed, which became more pronounced after 48 hours. The shift to the left within the granuloeyte ceil lineage three treatment-related deaths: fulminant hepatitis, hepatic observed in the differential blood count was less pronounced and eosinophils were failure and exacerbation of diabetes insipidus. also activated, No significant alterations in mucositis according to WHO classifications were observed either with G-CSF or with GM-CSF administration. Dose intensity of the CHOP-MEVP sequential therapy was Erythropoetin alpha (standard dose 100 international unTte per kg of body weight, administered subeutanously for a maximum of 8 weeks) led to an improvement in almost double to the standard CHOP therapy. G-CSF is haemoglobin levels in only 4 of 9 patients and obviated the need for transfusions. - useful for increasing dose intensity with minimizing Due to these effects, it was necessary to interrupt radiation treatment in only 3 of the 104 patients. In other 4 patients the carboplatin dosage had to be reduced it hematoIogic toxicities. was not necessary to terminate treatment in any of the patients. - Conclusion: First 352

time we could present that the application of G-CSF and GM-CSF as adjuncts to ge was 38.6+5.7 years. PCT was carried concurrent chemo-radiotherapy in the treatment of head and neck cancer is a good possibility to control leucopenia, which is one of tl~e most common side effects of this out according to the existing pr@grams. treament. So it is possible to treat without interruptions or dose reductions about the Leukopemia ~eveloping 0.5-2.0-I0~/I whole time of therapy. Despite erythropoetin, anaemia is frequent an indication for (1.3+0o2.10~/I), Sandoz Leukomax was admi- transfusions. Regarding mucositis, further observations, in as far as possible with nistered at daily doses of 5 to 8 mkg/kg objective parameters, will be required to provide additional information on the degree intravenously during 4-5 days. An increase to which the activation of granulopoesis and macrophages can be utilised to effectively treat damaged mucous membranes of the upper aerodigestive tract. of the blood l~ukocyte level up to 4-7.109 /i (5.6+1.2.1OVa)was seen after using the preparaYiom for 3-4 days. Acute cardiac insufficiency in I female patient, transi- USE OF rhg~-CSF (FILGASTRIM) IN CHILDHOOD ent thoracic and muscular pain and tempe- 68 SOLID TUMORS rature rise to 38~ in 9 patients were no- *S.Bartolozzi,M.D., A. Schlavetti,M.D., M. Iaeabinl,M.D., E. ted as adverse reactioms. Properzi,M.D., T. Notarantonio,M.D., and M.A. Castello,M.D. Use of Leukomax made it possible to com- Department of Pediatrics plete a PTC course at a normal regimen for University "La Sapienza" Rome, Italy 7 patients and to start a planned success- ive PCT course for 3 patients without re- Human recombinant granulocyte colony-stimulating factor (rhG-CSF) has been curring to hemocomponent therapy. sueeesfully used to prevent or reduce the duration of oeutropenia and We conclude that Leukomax is a valuable associated infections in cancer patients. tool in PCT courses for patients. patients and Methods: Ten patients (6 F, 4 M), with an average age of 7.2 years (range: 2 to 14 years), affected with solid tumors, were treated with rhG- CSF (filgrastim) during neutropenia induced by ohemo- and/or radiotherapy. All patients were afebrile and had normal eardiae, renal, and hepatic function. Patients with absolute neutrophil counts (ANC) less than or equal to 0.7xt09/L received a daily intravenous injection (5~glkg) of rhG-CSF for five days, beginning 24 hours after drng-induced aplasia. Results: As shown in the table, rhG-CSF administration resulted in an increase in the ANC. The mean ANC after five days of therapy with rhG-CSF was 4.5x109/L 70 THE EFFECT OF RECOMBINANT HUMAN (range: 2.5-6.5x109/L). Subsequently, the ANC fell, but never below 1.0xl09/L. ERYTHROPOIETIN (r-HuEPO) IN THE It was previously demonstrated that neutrophilic function increased in these TREATMENT OF CHRONIC ANEMIA patients alter rhG-CSF administration. In fact, rhG-CSF causes an in vivo SECONDARY TO CHEMOTHERAPY increase in 02" production by neutrophils stimulated with receptor-mediated WITHOUT CISPLATIN agonists via G-protein (e.g. with fMLP). None of our patients presented fever or Milidevid N., Vuleti~ L., Radulovid S., Bo~njak S. infections due to chemo-induced neotropenia. No temporary interruption or Institut za onkologiju i radiologiju Srbije reduction of antineoplastie drug dosage was necessary. No side effects occurred. Belgrade, Yugoslavia Conclusions: The severity and duration of chemotherapy-induced neutropenia was reduced by rhG-CSF, and there was an increase in neutrophilie function in The etiology of anemia in patients (pts.) with malignant diseases is vivo. Moreover, our data showed that rhG-CSF seemed to prevent morbidity and still unknown. It has been shown that the production of mortality due to infections. Therefore, rhG-CSF can be used to prevent delay in erythropoietin, as a kidney response to anemia, is insufficient in chemotherapy, and to eventually increase antineoplastie drug dosage as a result these types of pts.: ]evel of erythropoietin in blood serum is lower of the reduction of infections. than the level noted in pts. with the same degree of anemia who do case sex/age diagnosis ANC day 0 day 5 not suffer from malignant disease. The objective of this open, 1 F/6 Wilms 0.7 3.5 2 F/4 Rhabdomyosarcoma 0.5 3.5 multicentric, non-comparative study, in which our Insitute 3 F/14 Sehwannoma 0.7 4.5 participated with 10 pts.. was to evaluate the effect of subcutaneous 4 M/9 Medulloblastoma 0.6 5.5 rHuEPO (150 U/kg sc, 3 times a week, for a period of up to 16 5 F/5 Astrocytoma 0.7 6.0 weeks) on hematological parameters and transfusions requirements, 6 W10 Medulloblastoma 0.6 3.5 in pts. with chronic anemia (hemoglobin level, Hgb -<10,5 g/dl) 7 F/11 Medulloblastoma 0.6 2.5 secondary to cancer and cyclic chemotherapy. During the 1993. the 8 M]6 Hepatoblastoma 0.7 6.0 9 M/2 Rhabdomyosarcoma 0.7 6.5 study included 10 pts. aged from 20-62 years (median age 45.4 years), 10 M/5 Neuroblastoma 0.6 3.5 with ECOG performance status of -< 3. all with clinically stable disease for one month preceding study entry and a life expectancy of longer than three months. 4/10 pts were with lung cancer. 3/10 with carcinoma of the breast, 1/I0 had malignant melanoma, 1/10 had osteosarcoma and 1/10 had fibrosarcoma. Patients with acute leukemias, malignancies derived from myeloid cell line, anemia ~zA z~ ONCOT,OO~Zr Paezmws n~W- atributable to causes other than cancer and chemotherapy ( vitamin LOPEn DU~INa PROG~ POr,ZCa~IO- B12, folate or iron deficiency, bleeding or significant hemolysis) were not included in the study The average value of Hgb before study entry was 7,9 g/dl (range 4,9 - 9,6). 8/10 pts were evaluable for *Ye.P.Svedentsov, Z.D., cfficacy of rHrEI'O. A favorable therapeutic effect (an increase -> 2 N. Z. Sherman g/dl in Hgb level) was achieved in 6/8 pts. After 3.6 wks. (range 1-7) The Research Ir~stitute of Haematology -:l~d of r-HuEPO administration, Hgb rised by 3,3 g/dl (range 1.7-5.6) Blood Transfusion, Kirov, Russia such that the average post-therapy Hgb value was 12,1 g/dl (8,5 - 15,0 g/d0.9/10 pts completed the study. The rHuEPO therapy lasted an Observations were perfoymed on 10 pati- average of 8,6 wks., with two patients treated during the entire 16 ents: 4 with carcinoma of the lactiferous wks duration of the study. During the administration of rHuEPO, gland ~gNgE~-T~N^, ,N~, 4 with lymphogra- there was no need for erythrocyte transfusions. Side effects were not nulomat~s~s~ 1~w~)c~rcinoma Of the ovary, noted, rHuEPO has a favorable therapeutic effect on anemia in I with trophoblastic disease. The age ran- cancer patients treated with repeated cycles of chemotherapy. 353

FIRST CASE REPORT OF TOTAL BONE 73 THROMBOCYTOPENIA AFTER CHEMO- 71 MARROW (BM) APLASIA AFTER HIGH- THERAPY AS AN INDICATION FOR SE- DOSE CHEMOTHERAPY AND PERIPHERAL QUENTIAL APPLICATION OF INTERLEU- BLOOD PROGENITOR CELLS (HDCT-PBPC) IN A 53 YEAR OLD FEMALE WITH HIGH- KIN-3 (IL-3) AND GRANULOCYTE-MACRO- RISK BREAST CANCER. PHAGE-COLONY-STIMULATING FACTOR C.Duhem, F.Ries, MD, M.Dicato, MD (GM-CSF) Department of Hematology-Oncology, Centre *Dimitrios Chatsiproios, M.D., Lothar F~rber, M.D., Hospitalier de Luxembou rg, L- 121 (| LUXEMBOURG Christian Schweiger, M.D., Hans Schmid, M.D., Hermann Krieg, M.D., Department of Gynecology, Hospital Heilbronn; We report on a 53-year old woman treated for locally advanced Clinical Research, Sandoz AG, Nuremberg; Department of breast cancer (T4 N1 Me). Her treatment began with Gynecology, Medical School Heidelberg; preoperative chemotherapy (CT) consisting in 4 courses A 59-year old patient with metastatic breast cancer (stage Cyclophosphamide (CPA), 600 rag/m2, Mitoxantrone 10 rag/m2, 5-FU, 600 rag/m2) followed by intensive CT (Carboplatin 900 III ductual carcinoma) underwent myelotoxic chemotherapy rag/m2, CPA 5 g/m2, Melphalan 50 rag/m2) with PBPC support. (Mitomycin C 8 mg/qm, dl, 5-FU 750 mglqm, d1+2). In PBPC quantification was made on the basis of mononuclear cell spite of prophylactic use of G-CSF (Granutocyte-colony- (MNC) count in a sample (1,7 x l0 s MNC/kg). The PBPC were stimulating factor) the patient exhibited severe persistent reinfused, 12 hours after CT. pancytopenia. As no signs of spontaneous bone-marrow 3 weeks post-CT aplasia, recoveD" was normal for WBC, and very slow for RBC and platelets. Nevertheless, surgery and recovery could be observed, we started sequential applica- radiotherapy were performed according to the planned program. tion of tL-3 (5 pg/kg/day for 5 days) fotlowed by GM-CSF Ten weeks after CT, a severe BM aplasia and is still persisting (5 pg/kglday for 5 days). The thrombocyte counts increa- for more than 1 year after successive lines of treatment (G-CSF sed steadily from 14.000/pl to 121.000/pl after the IL-3 and and EH-thropoietin, high-dose Dexamethazone, IL3 followed by GM-CSF). GM-CSF treatment and remained almost constant on that Several hypothetical mechanisms can explain this unusual level. 4 weeks later, after the next cycle of chemotherapy, complication : idiosyncratic reaction to a cytotoxic drug, the patient was treated prophylacticly with IL-3 and GM- irreversible injury tu the early stem cell at a given phase uf the CSF. As a result, no pancytopenia occured. Side effects procedure (after a phase of maturation of the committed due to IL-3 administration (flu-like symptoms) were typical progenitors in the PBPC), cumulated toxicity of combined treatments... Whatever the mechanism, this possible complication of growth factors and could be treated effectively with Para- of HDCT-PBPC should be continued to be looked for. cetamol. These data support the additive efficacy of se- quential application of IL-3 and GM-CSF in chemotherapy- induced thrombocytopenia. Supported by the data available from recent studies we conclude that thrombocytopenia after myelosuppressive therapy can be an indication for the 72 INTERLEUKIN-3 (IL-3) IN THE THERAPY application of IL-3 and GM-CSF. OF APLASTIC ANEMIA (AA) *Lothar F~irber, M.D., Christian Schweiger, M.D., Ulrike Haus, M.D., Theresa Schaechtl, 74 INTERLEUKIN-3 (IL-3) AND GRANULO- M.D., Hermann Wagner, M.D., Clinical Re- CYTE-MACROPHAGE-CO LONY-STIMULA- search Sandoz AG, Nuremberg; Medical De- TING FACTOR (GM-CSF) 1N OSTEOMYE- partment, Hospital Weiden LOFIBROSIS INDUCED MYELOSUPPRES- We report on a 66-year old female patient with rheumatoid SION arthritis who developed severe pancytopenia with petechial *Christian Schweiger, M.D., Lothar F~rber, M.D., UIrike bleedings after application of azathioprin. During the thera- Haus, Ph.D., Mathias Hauser, M.D., Gerhard Meuret, M.D., py with corticosteroides the patient needed 7 platelet and Clinical Research, Sandoz AG, Nuremberg; Medical Clinic 12 erythrocyte transfusions. No substantial increase in gra- St. Elisabethen, Ravensburg nulocytes and thrombocytes was observed in the following We report on a 49-year old patient with osteomyelofibrosis treatment with 5 pg/kg/day G-CSF (Granulocyte-colony-sti- who showed pronounced myelosuppression accompanied mulating factor). Therefore we started rhlL-3 at a daily by petechial bleedings. Since the thrombocytopenia per- dosage of 5 IJg/kg subcutaneously. The thrombocyte sisted even under continuous transfusion therapy with HLA- counts increased from 5.000/pl to 61.000/pl five days after matched thrombocytes over 10 days, we started an inter- the beginning of IL-3 therapy and stabilized at a level of ventional therapy by giving rhlL-3 subcutaneously at a 145.000/pl. No transfusion therapy was needed, and no dosage of 5 pg/day/kg body weight. Although thrombocyte bleeding complications occured. IL-3 therapy was well tole- counts persisted during transfusion treatment in the range rated, no side effects due to IL-3 could were observed. This of 10.000lpl to 19.000/pl, under IL-3 a significant increase case report demonstrates the potential benefit of the appli- in platelets to 32.000/pl was observed already five days cation of IL-3 in the therapy of severe pancytopenia, espe- after start of IL-3. For long-term treatment of leukopenia cially in case of thrombocytopenia. While therapy with and thrombocytopenia the patient received rhGM-CSF G-CSF showed no response on myelopoiesis, the applica- (5 pg/kgtday) in daily alternation with IL-3. The frequence tion of IL-3 could succesfully prevent any further transfusion of HLA-matched thrombocyte transfusion dropped from 10 therapy and bleeding complications. per day to 1 per week without any bleeding complications. 354

No side effects due to rhlL-3 or rhGM-CSF administration Material and methods: After finishing the normal treatment (including operations, could be observed within three months of therapy. The chemotherapy, irradiation) 30 patients (25 men, 5 woman) with head and neck data support evidence for efficacy and safety of long-term cancer (stadium 4 UICC) got 0.5 mg/kg body weight 13-cis-retinoic acid application of rhlL-3 and GM-CSF in case of myelosuppres- (Roaccutan (R)) daily and 3 million IU interferon alfa (Roferon (R)) three times sion. A cumulative effectiveness of IL-3 and GM-CSF is every week about max. 6 month. Clinical and paraclinical investigations were supported by the results of Ongoing studies. We conclude done every 4 weeks, a completed staging every 3 month. that in cases with thrombocytopenia IL-3 can be effectively Results: In 16/30 patients the treatment was carried out about 6 month. These combined with GM-CSF. patients had no recurrent tumor. 4 men finished the treatment without recidive because of the side effects. In 10 patients we have seen a recurrent carcinoma. That's why the combination therapy was finished previously in these individuals. 75 EFFECTIVE TREATMENT OF CHEMOTHE- Main side effects were fever (30 %), mucositis (88 %) and moderate increased RAPY INDUCED SEVERE THROMBOCY- hepatic encymes (30%). TOPENIA WITH INTERLEUKIN-3 (IL-3) Conclusion: These first presented preliminary results indicate that the usage of *Lothar F~rber, M.D., Christian Schweiger, interferon alfa and 13-cis-retinoic acid is a good possibility for the adjuvant M.D., Glenn FLichsel, M.D., Jens-Uwe Traut- treatment of patients with head and neck cancer in stadium 4 (U!CC), who have vetter, M.D. a high recurrence rate normally. Clinical Research, Sandoz AG, Nuremberg; Department of Gynecology, Halle University A 60-year old woman with abdominal carcinoma of un- known origin was treated with 6 cycles of EAP-chemo- therapy (Cisplatin (70 mg), Adriamycin (35 mg), Etoposide PERIPherAL BLOOD LYMPHOCYTE POPU- 77 LATIONS AND PHAGOCYTIC FUNCTIONS (210 mg)) without response. The second chemotherapy IN CHILDREN WITH BRAIN TUMOR with Carboplatin (960mg) and Cyclophosphamide (560mg) TREATED BY LEVAMISOLE had to be stopped after 1 cycle because of severe pancyto- *Tomislav Franjo Hajn~i~,M.D,Josip penia. After 4 months regeneration the third chemotherapy Lukat,M.D.,Tajana Hajn2id,M.D. with Etoposide (630 mg) was administered once. Severe Dpt. of Pediatrics, Clin. Hospital myelosuppression occured again. Since thrombocytopenia Sestre Milosrdnice,Zagreb, Croatia persisted and remained refractory to transfusion therapy, it Complex disturbances of immunity in patients was decided to start an interventional therapy with interleu- (pts)with malignant diseases are considered kin-3 (5pg/kg/d) for 12 days. responsible for increased infection rate and Results: After chemotherapy the thrombocyte counts drop- more frequent appearance of relapses.The au- ped to 16.000/pl. By starting IL-3 a steady increase in the thors have been studied Levamisole(Le)asso- thrombocyte counts could be achieved to 68.000/pl (day 7) ciated alterations of immunity in children and 129.000/pl (day12). No side effects due to IL-3 were with brain tumor(BT).PATIENTS AND METHOD.Pts with ST aged 2-14 years received Le 2,Smg/kg observed. body weight p.o.for three consecutive days Discussion/Conclusion: This report demonstrates the effica- every two weeks for 6-12 months. T lymphocy- cy of IL-3 in chemotherapy induced thrombocytopenia. tes(ly),B-lylthe proportion, P andabsolute Whereas multiple thrombocyte transfusions are not effec- number,ANxl0J/L),the ingestion(li)and intra.- tive, megakaryopoiesis can be stimulated sufficiently by cellular killing capacity(KC)of granulocytes IL-3. We conclude that thrombocytopenia as a dose-limiting (G) and monocytes (Mo) were determined by method reported earlier(Lukat at ali.1983). side effect of chemotherapy represents an indication for the RESULTS.Phagocytic activity was significant administration of IL-3. better and number of immunocompetent cells was higher in Le treated pts with BT.Table. The incidence of infection has been dimini- shed during the administration of Le. CON- 76 13-CIS RE'TINOIC ACID AND INTERFERON ALFA IN THE CLUSIONS. Le,immunomodu].ating adjuvant drug ADJUVANT TREATMENT OF HEAD AND NECK CANCER stimulate immune response in immunocompromi- sod pts with BT. *Jens BLinlzel, M.D., Klaus KQttner, M.D. Department of ENT Non Le-treated Le-treated Klinikum Suhl/Th(Jringen N x N x D 98527 SuN, Germany G I i 21 2 79 14 3,40 CP 21 6 77 i4 7,36 21 0 94 14 1,15 Introduction: Unknown microscopic residual tumors are the reason of fast ''~~',", Ii CP 21 41 08 14 50,00 developing recurrent carcinomas in patients with head and neck cancer In the ~.~ ly P i0 0 43 9 0,57 presented study we used the combination of interferon alfa and 13-cis-retJnoic T 1y P i0 0 61 9 0,51 acid to protect these patients against the recidive, induced by the positive AN i0 1 37 9 1,92 results of this combination in the treatment of recurrent squamous cell _~ Iy P 10 0 09 9 0,14 carcinoma, recently published by Lippman and other autors. AN !0 0 18 9 0,51 355

Transdermal Fentanyl Should Be Titrated Pain intensity (Pl) assessment was performed by a trained investigator at 78* On A Day To Day Basis In Well Monitored time intervals of I/2, 1, 2, 3, 4, 5, 6 hours after dosing or until rescue Patients With Uncontrolled Cancer Pain medication. PI was evaluated using a VAS ranging from 0 mm (no pain) *W. Korte MD, N. de Stoutz MD, R. Morant MD to 100 mm (unbearable pain) together with a 4-point verbal scale (none, mild, moderate, severe pain). Efficacy data are not yet available due to Kantonsspital, Inst. for Hematology and Div. of Oncology, 9007 St. Gallen, Switzerland the double-blind study design. To date no withdrawal for toxicity has been documented. Enrollment will be completed by the end of June 1995. Up to now 170 of the planned 180 patients have been randomized Initial dose finding in pts. with cancer pain started on "ITS Femanyl and complete data on efficacy and tolerability of the two treatments will (Duragesic TTS-F) is often unsatisfactory with the doses/dose intervals TM, be presented at this meeting. recommended. Acknowledging studies revealing a pseudo stead)' state 15 h after application, we prospectively investigated an increased initial dose (150%) and day-to-day titration for initiation of TTS-F in pts. with uncontrolled cancer pain. In 39 evaluable pts. during an initial 28 day 80* CLINICAL AND RADIOLOGICAL EFFECTS stud) period, significant reduction in pain intensity (p = 0.001) was seen at OF PAMIDRONATE IN BREAST CANCER- 24 h and stable analgesia was achieved within 48 h. Significant increases INDUCED OSTEOLYSIS. in TTS-F were necessary during weeks l to 4 to maintain pain control, but *J.J. Body, B. Vanderschueren, J. Alexiou, no evidence of tolerance was seen. Pain control in opioid-naive pts. was not M. Piccart, J.C.Dumon. Rehabilitation & Supportive Care Clinic and Dept Mean Values • Simple Standard Deviations of Radiology, Inst. J. Bordet, Brussels, Belgium. treatment VAS TTS-F Morphine days (ram) (m~d) Initial results obtained with the bisphosphonate before 54 5:21 65 • 87 # pamidronate (Pam., Aredia| for the treatment of painful day I 39 5:29 45 • 36 17 +_ 27 V metastatic bone disease are encouraging. We treated 24 day 2 29 _+ 25 53 + 43 19 • 30 V patients (pts) with breast cancer and extensive bone day 7 23 • 22 92• II• metastases by 90 mg Pam. infusions every 4 (3-8) weeks. day 14 21 • 112• 13 5-23V Seventeen pts also received systemic antineoplastic day 21 21 :t: 24 1265:117 8• therapy, but therapeutic failure was evident in at least 9 of day 28 25 • 23 138 • 122 7 • 15 V them. Pain was graded into 4 categories (none, mild, # = regular dose V = rescue mcdication moderate, severe). Of the 17 pts who had bone pain, 16 (94%) showed some degree of improvement; of the 14 pts different from that in pretreatcd pts. 49% of the pts. received early (< 72 h) with moderate to severe pain, 7 became pain-free. There dose increases. One none-compliant patient had severe side effects partially was, however, no evident decrease in analgesic due to the specific properties of the TTS. Other side effects, most of all consumption, which was probably due to an increase in constipation, seemed less common compared to usual morphine therapy. activity and mobility. This was substantiated by the fact that Post study long term follow up treatment was applied up to 408 days in a the performance status (PS, ECOG scale)improved in single patient, with overall 3542 treatment days. TTS-F can and should be 10/24 pts (42%). A CT-scan of a target lesion was titrated effectively and safely on a day to day basis with a ldgher initial performed every 3-4 months and, for study purposes, dose with adequate patient monitoring to provide stffficient pain control evaluated by a radiologist who was unaware of the early, thus easing it's use and avoiding more complicated approaches. sequence of the examinations. Densification was observed in 10/24 pts after a median of 6 Pam. courses. When considering only the pts who had never received radiotherapy on the target lesion and the pts who had a A DOUBLE-BLIND STUDY I"O COMPARE TWo SINGLE- clear tumor progression, densification was still observed in 79* DOSE REGIMENS OF KETOROLAC (10 AND 30 MG I.M.) WITH DICLOFENAC (75 MG I.M.) tN CANCER PAIN. 5/11 pts. The clinical meaning of these radiological *V. Minntti t, M.D., G. Cic,r I, M.D., M. Betti I, M.D., M. changes remains, however, unclear, as they were not Bagolan2, M.D., P. Dominici2, M.D., M. Tonatot, M.D., G. evidently related to the improvements in pain or PS. In Fumi3, M.D., A. Dr Favero3, M.D. summary, iterative pamidronate infusions in breast cancer ~Division of Medical Oncology, ~Instituteof Internal Medicine, Perugia Hospital; :Clinical Dew Recordati, Milan, Italy. pts with extensive bone metastases exert clinically relevant analgesic effects in most pts and induce densification of Non-steroidal anti-inflammatory drugs (NSA1Ds) are usually prescribed lytic lesions whose exact significance remains, however, to as first-line drugs for mild m moderate cancer pain. It has been be established. demonstrated that Ketorolac is as efficacious as morphine in the treatment of acute cancer pain, but the optimal dosage is still open to controversy: it is an important issue due to Ketorolac dose-related side CLODRONATE: RELIEF OF BONE effects. No clinical trial has compared Ketorolac to other widely used 81" PAIN IN METASTATIC CANCER NSAIDs (such as Diclofeuac) for the same indication; this prompted us to evaluate in a double-blind study the efficacy of two different doses of * Jaroslav Shparik, M.D. Ketorolac (10 and 3O nag i.m.) in comparisonwith Diclofenac (75 rag Dept.Oncology, P.O.Box 2468, Lviv, i.m.), one of the most widely used NSAIDs in cancer pain. Hospitalized 290029, Ukraine cancer patients suffering from moderate to severe pain (at least 40 mm on a 100 mm visual analog scale, VAS) are eligible for the study if they have not received any analgesic treatment in the previous 4 hours. Patients with NSAIDs hypersensitivity, renal function impairment, Many patients (pts) notice significant improvement in thromboc31openia, active peptic ulcer, gastrointestinal bleeding, or relief of bone pain when bisphosphonates is used for receiving other drugs which could influence analgesia are excluded. cancer-associated hypercalcemia. To evaluate this 356

pain-relieving effect a preliminary study was initiated PAIN INTENSITY AND THE "ANALGESIC to evaluate the affect on pain in pts with metastatic 83* LADDER" IN PEDIATRIC ONCOLOGY. cancer without associated hypercalcemia. From April 1994 through January 1995, 46 pts were given 1.5 g G.Ragni, A.Antimi, A.Sehiavetti, A. Minofi, A. CIerico. clodronate (Clasteon) iv in 500 ml normal saline over Ontology Service, Pediatric Clinic, University of Rome "La Sapienza" 5 h or 300 mg iv daily for 5 consecutive days. This was repeated monthly, if significant improvement in pain occurred and there was still room for The three step "analgesic Ladder", proposed by an expert committee convened by the Cancer Umt of the World Health Organization, emphasizes that pain improvement. It was discontinued if no significant intensity should be the prime consideration in analgesic selection. Self evaluation improvement occurred or with total resolution of pain. and behavioural scale could be helpful to assess pain as mild, moderate, severe Primaries include breast 26, lung 12, prostate 2, and address the treatment according to the analgesic ladder (NSAIIN for mild pain, weak narcotic for moderate pain, strong narcotic for severe pain) . myeloma 4, colon 1, unknown 1. 34/46 (74%) Quantification of pain in children is difficult expoeiallyin youngerpreverbal child. noticed significant pain relief, decreased narcotic In our Service the different intensity of pain experienead by children with cancer has been assessed with a hetero-evaluation and a self-evaluation. The first, a requirements and improved quality of life. 12/46 Karnofsky method modified for childhood,is based on health care professional (26%) were not able to tell any significant difference, observations concerning specific pain behavior, and laboratory and radiographic while none noticed an increase in pain or narcotic examination. The second consists in pain measurements based on patients self reports ( Huskisson's colorimetric scale and facial analogue scale). Self requirements. No major toxicity with clodronate was evaluations are limited to the child who is old enough to understand the testing noted. There was no interaction with concomitant procedure for extn'essinghimself or herself in a standardized and reproducibile radiation therapy, or chemotherapy. There were no fashion; in the preverbal child the evaluation must be based entirely on parental report and physician observations and examination. Youngestchildren bone marrow suppression, coagulopathy nor may express their pain with the "affective facial scale", the oldest ones with the significant renal dysfunction. Clodronate would "Hnskissen colorimetric grade'. These two different methods of evaluation give appear to be a useful supportive drug in the us the broadest possible data with which to formulate a treatment plan, according to the WHO. The formhas been completed every day from the beginig of pain to management of tumor-related bone disease. the end of the drug administration. Fortysix children entered (61% male, 39% female), aged between 3 mos and 22 yrs (meert 10.3 yrs): 6.5% were less than 3 yrs, 50% were aged between 3-9 yrs, 17.5% between I0 and 15 yes, 26% between 16-22 yrs. Hetereevaluation was performed in all patients, self evaluation in 43 patients (93.5%). Pharmacological treatment was effective in 90.8%, persistent pain eceured in 9.2%. ha 4 patients, pain relief was obtained after palliative chemotherapy. In 5 patients (10.8%) the self-evaluation revealed a grade 2, but heteroe~luation showed a grade 1. Pain relief was obtained after 82* PATIENT CONTROLLED ANALGESIA (PCA) NSAU) administratiorL Most of these patients were aged between 3 and 9 years. IN CANCER PATIENT The over-self evaluation is probablyrelated with the young age and the parental anxiety. In 16.4% of all self evaluated patients (43), self evaluation showed a '~Lossignol D., M.D., Bredas Ph., M.D., grade 3, but heteroevaluation revealed a grade 2. Pain was relieved with strong Obiols M., R.N. narcotic. Most of these patients (91,5%) were young adult (16-22 yrs). Eudorphines dosages showed in these patients high values, and slowly returned to Unit~ de R6habilitation, lnstitut Jules Border normal after drug administration. In patients less than 3 yrs of age, Brussels, Belgium heterocvaluatiun was not significantly related with intesity of pain. Acknowledgement: This study is supported by CNR ACRO n.94.01110.39

PCA is an interesting alternative route for analgesics administration. It is widely used for post operative pain using the subcutaneous (SC) route. SUPERIOR HYPOGASTRIC PLEXUS NEUROLYSIS 4* FOR PELVIC CANCER PAIN We used PCA in 33 cancer patients with solid tumors There are 14 intravenous *Maciej Hilgier, M.D.,Ph.D., Jerzy Jarosz, M.D., (IV) treatments, 17 intrathecal treatments (IT), 1 SC treatment and I peridural (PD) treatment. Ph.D. Dept. of Anaesthesia, Cancer Pain and Palliative The main indications were: intolerance to systemic administration and well Treatment Center localized pain for IT (and PD), incidental-breakthrough-pain or high doses of Maria Sklodowska-Curie Memorial Cancer Center - analgesics required for IV (and SC). The drugs used were morphine in all cases Institute of Oncology, Warszawa, Poland fentanyl or sufentanyl and bupivacame for the IT route, and ketamine (only IV) in 3 cases (doses and schedules wilt be developped). Aim: To evaluate the effectiveness of superior hypogastric plexus neurolysis in the control of pelvic cancer pain. Adequate pain relief(Visual Analog Scale < 3/10) was achieved in all cases Methods: Twenty-four patients with low abdominal and perineal pain during a period of more than 3 months. Nevertheless, all but 1 of the patients sccondary to advanced cervix cancer (12), uterine body cancer (4), and with IT treatment required a systemic administration because of poor pain prostatic cancer (6) were referred to SHPN. All patients had undergone control: progression of the disease, medullar toxicity, new painful localization, previous pain relief methods such as radiation therapy, chemotherapy and terminal illness The ease of use of PCA allowed patients an adequate pain control despite those events. pharmacological medication according to WHO "step II" + anticonvulsants and antidepressants and experienced visceral and neuropathic (mainly It is interesting to note that morphine alone (IV) provided the best response in burning) pain of an 8-10 intensity on visual analogue scale (VAS). All 25 cases, and that the use of ketamine was necessary only in 5 cases On the 33 diagnostic blocks and neurolysies were performed with the patient in the patients, only 8 were not able to go back home. We did not experimented local lateral, left side up, position according to our previously established method. or technical complication. Results: After prognostic blockade the analgesic effect was good in all the cases (VAS 1-4). On the day after neurolysis 19 patients estimated the PCA in cancer patients offers a safe and effective alternative for analgesics intensity of pain as VAS 1-4 and 5 patients as VAS 5-7. This latter group administration Our experience suggest that the IV route remains the route of received SHPN on the collateral side. The following day all patients but one choice for a long term pain control. in this group experienced good pain relief (VAS 2-5). Two weeks after 357

neurolysis all the patients had pain intensity below VAS 5, some of them, There are 3 grades: (I) good prognosis, (II) intermediate and (III) bad however, received ,,weak opi0id" analgesics. Three months after nenrolysis prognosis. Using the ES, we first received 49 charts of cancer patients with solid 17 patients estimated the pain intensity as VAS 4-5, 2 as VAS 6-7 and 4 as tumors. All but 2 were ranged at grade III but only 5 experienced difficulties for VAS 7-9. All these patients simultaneously received previously applied complete pain control (Visual Analog Scale > 4/10). analgesics although not exceeding the entry dosage. The "VAS 6-7" patients refused morphine while the WAS 7-9" patients received oral morphine. We prospectively followed 39 cancer patients (l 7 female, 22 male -age range: There were no side effects nor any complications due to the 34-86). There were 38 solid tumors and 1 hematological disease. All but 3 were blockade/neurolysis. In 5 cases the procedure was difficult and demanded 2- at grade III, essentially because incidental pain (item 2) and history of 3 corrections of the needle trace. toxicomany (item 7). Nevertheless all of those patients experienced good to Conclusion. Our results demonstrate that SHPN has good immediate excellent pain control after 8 days of follow-up. Despite treatment schedule analgesic effect. In the three months of follow-up SHPN provided a decrease adaptations, results remains good after 1 and 2 months. in pain intensity although it was not possible to lessen the initial dosage of Regarding those results, it appears that the ES is too sensitive to detect patients analgesics. with bad prognosis in terms of pain control. Other items should be taken into SHPN may be counted among the effective methods in the strategy of pelvic account: type of neuropathic pain, sleep quality, number of pain sites, time cancer pain control. between the onset of pain and the first treatment.

It is also possible that the multidisciplinar approach of pain syndromes is the best ~'/t' FROZEN SHOULDERIN BREASTCANCER: way to avoid bad pain control in cancer patients. A NEW APPROACH A prospective study using new items is actually conducted at our institution. *Maquet Ph, KT., Lossignol D., M.D., Bredas Ph.~ M D. and Obiols M., R.N Unit6 de R6habilitation, Institut Jules Bordet Bmssels, Belgium OPIOID USE, TREATMENT DURATION AND Frozen Shoulder Syndrome is a complication observed among patients with 87 breast cancer after surgery (radical mastectemy or lumpectomy) and radiation CHARACTERISTICS IN 466 CANCER PATIENTS therapy. There is no effective, medical treatment for this syndrome. WITH PAIN. A RETROSPECTIVE ANALYSIS. Manipulation under anesthesia offers new perspectives of treatment and allows D. Simonsen, R.N., I. Mejlhoim, *M. Kjaer the patient a better quality of life. We treated 10 patients with breast cancer P. Vejby Hansen. (age range: 45-65), 7 had a radical mastectomy and 3 lumpectomy. All but 4 Clinical Oncology Research Unit. Dept. of received post-operative radiation therapy. The frozen shoulder syndrome was Oncology, Aalborg Hospital, DK-9100 confirmed by physical examination and X Ray films. Aalborg, Denmark. None experimented adequate medical treatment. Functional, pain and psychological evaluations were performed using complete articular and muscular The clinical course and prognosis for cancer patients testing, HAD scale and VAS for pain (global, nadir and acme). with pain has been the subject of a number of reports mainly from pain clinics. Few reports are available Manipulation respecting physiological moves &the shoulder was performed from oneology depts, with a well-defined area of up- under loco-regional anesthesia (Interscalene brachial plexus block with take covering the complete clinical course of a signi- bupivaca[ne, fentanyl and tnamcinolone) on day O and a complete evaluation ficant number of patients. The Oncology Center in was achieved on day 1, 10 and 30 and after 3, 6 and 12 months. Aalborg has a population background of app. 600.000 All but 2 patients completely recovered (in terms &function and in terms of pain inhabitants and is responsible for the diagnosis, relief). The 2 other patients presented a complete pain relief but recovered only treatment and follow-up of app. 10% of Danish cancer at 70% in terms of function. patients. In the 3-year period of 1989 through 92 :This was confirmed after long term evaluation (12 months and more). 466 cancer patients had their terminal course and died yurthermore, pain medications were no longer necessary. in the Dept. of Oncology. 427/466 patients, app. 92% received pain therapy in the course of their disease. Manipulation under loco-regional anesthesia in frozen shoulder syndrome is a Pain therapy was consistent in the period and given new approach which offers a rapid pain relief and a long term adequate function. according to WHO guidelines. The median age of the It may be realized in an in -, and out-patient setting. Further studies are still population was 61y (18-88y). The tumour types were necessary to detect patients at risk and to determine those who can benefit from lung 24%, breast 19%, gynecol, malignancies 18%, G-I this technique. tract cancer 8%, urological malignancies, head and neck + unknown primary, malignant lymphomas 7% each, and other types 10%. All patients had pain from their 6 A STAGING SYSTEM FOR CANCER PAIN malignant disease and were in an advanced stage. Per- Obiols M., R.N, *Lossignol D., M.D. formance status (WHO) at start of therapy was 0-7%, 1-22%, 2-33%, 3-18%, 4-16% and unknown 4%. Median min. Unit6 de Rehabilitation dose of non-opioids 0 (O-Sg) daily, median max. dose Institut Jules Bordet 4 (0-6g) daily. All opioids were converted to oral Brussels, Belgium morphine. Median min. dose 30 (0-2.000mg) daily, median max. dose 400 (0-72.000mg) daily. G-I tract The <~ Edmonton Staging System )> (ES) for cancer pain is a seven items scale cancer had the highest consumption of opioids and the designed to determine the prognosis of pain in terms of response to treatment longest duration of treatment. The median duration of (Bmera E, 1989). pain therapy from start until death for the whole group was 2 me. (a few days-92 mo.). In this retro- The seven items are: types of pain, incidental pain, doses of opioids required, spectively analysed material cancer patients with pain tolerance to opioids, psychological problems, psychiatric problems and history have a very short median survival and a considerable of toxicomany. variability in opioid consumption. 358

THE EFFECT OF PALLIATIVE RADIOTHERAPY peutic scale and in 73% of them a good pain 88 ON QUALITY OF LIFE IN CANCER PATIENTS control was reached (minor 3/10 by VAS). *Shulamith Kreitler, Ph.D., Felix Kovner Our results show that the great part M.D., Nami Peer, B.A., Orit Aronson, B.A. of patients with urologic malignancies re- Samario Chaitchik, M.D. main free of pain with sequential oral tre- Institute of Oncology & Department of atment, following the WHO guidelines; more Psychology, Ichilov Hospital and Tel- agressive therapy is only requiredin a Aviv University, Tel Aviv, Israel small number of them. In recent years there has been a growing concern with the quality of life of the patient with advanced cancer. Studies showed that many of these patients 90 THE MEASUREMENT OF PAIN INTENSIFY suffer from psychological distress related to pain and IN HOSPITALIZED CANCER PAIIENTS reduced physical performance (~aasa et al., 1993).The ~Juraj 8AUMOHL, M.D. PhO., purpose was to examine the effects of palliative M~ria WAGHEROVA, M.O. radiotherapy on the quality of life of patients with Oepartment of Radiotherapy and Onco[ogy advanced disease. Thirty patients (mean age 60.4 yr) UNIVERSIIY HOSPITAL L.PASTEUR with a variety of cancer diagnoses (bone, liver, 041 90 KO~ICE, SLOVAK REPUBLIC brain, breast etc.), all in stage IV of the disease, got palliative radiotherapy that lasted on the average 8.6 days, with an average intensity of 2000 Ihe treatment of cancer pain is important rad. Before and after the treatment the patients part of the treatment of cancer patients filled the following questionnaires: The Comprehensive The main basis for successful analgetic &ssessment of Quality of Life (Kreitler, Kreitler & treatment are assessment of cancer pain Chaitchik); The Profile of Mood States (McNair, Lorr ].rltensJty and evaluati, on of eL]el, oily of & Droppelman) and the Positive Emotions Check List cancer pain. Despite pain is subjective (Kreitler & Kreitler) assessing five negative and feeling, there are many methods to evalua- five positive emotions; the 5UNYA Revision of the te interlsity of pain. The purpose of our Psychosomatic Symptom Check List (Attanasio et al.); study were to evaluate the interlsJty of and the Cognitive Orientation Questionnaire of Health cancer pain among hospitalized patients assessing the motivation for health. The results -- using visual analog scale (VAS). based on analyses of variance, covariance and Methods: discriminant function--showed significant improve- From January to March 1995 we evaluated ments in the quality of life, emotional state (anxiety the irltensity of cancer pain among hospi- and depression but not anger), and physical symptoms talized patients at our 30 bed department. (especially pain) following radiotherapy. There were Results: no changes or effects due to motivation for health. 22% of the patients had no pain, 72% had The major conclusion is that palliative radiotherapy pain low intensity (VAS 0 - 5), 21% had is a potent means for improving quality of life of pain medium intensity (VAS 4 - 6), and advanced cancer patients. 7% had high intensity pair~ (VAS 7 10). Conclusions : VAS is a good tool for evaluation of can- cer pain and for monitoring effectivity of analgetic treatment. 9 "A STUDY OF PAIN RELIEV IN CAN- CER PATIENTS". Calvo J.I., Anad6n M-P., *Teje- dor M., Pezonaga L. 91 RESULTS OF AN OPEN-LABELLED Unidad del Dolor. Servicio de SEQD~NTI:iL STUDY OF MG1 209 FOR 0ncologla. CONTROL OF PAIN ASSO~AATED WITH Hospital de Navarra. C~]OTHs O~T~ MUCOSAL Pamplona, Navarra, EspaHa. ULCerATIONS Miodrag deki6,M.D., We performed a retrospective, descri~ Surgical Service,Clinical Hospi- live study about the features and intensity of pain in urologic malignancies. tal Centre,Zemun-Belgrade,YU During 1992-93, 71 patients of ages between 46 and 91 were treated for pain due The purpose of this study was to evaluate the efficacy of MGI 209 for control of pain to urologic malignancies (41 with prostatic adeno-c., 24 urotelial neoplasia, 3 hiper- associated with oral mucosal ulcers resul- nephroma, 2 epithelial carcinoma of penis, ting from treatment with cytotoxic aotineo- 1 testicular neoplasia). We assesed the pa- plastic agents. ttern and intensity of pain and the effici- Additionally,the duration of effective pain ency of the treatment. control was measured against the reteotion Ninety-nine percent of the patients of a single application of the agent. showed somatic pain and 15% neuropatic pain. Twenty subjects were entered from eight si- The mean value of intensity measured by vi- tes.65%of eotered subjects were female.The sual analoge scale (VAS) was 7/10. mean age was 55 years.The mean number of ul- All patients were treated according cers and ~ffected area per subject were2.6 to World Health Organization (WHO) there- and 2.9cm,respectively. Disease states were 359

determined to bel/3hematogologic and 2/3 Results : solid tumors. Baseline procedures were limi- Patients evaluable alter I mouth ted to establishing the level of ambient Totpop Horm Lung OtherHorm 1 (304) det~..end(90) :: (93) :. indel~end(121) oral pain,the levelof pain achieved with "'Prior"me'a'n'Wi'o';"s...... '"'4 :'3 5"kg ...... 3".'94"kg ...... Li:~/g k'g ...... 47}'i kg"...... the orangejuice stimulus and application of Mean Wgain monthl : 0.16kg 0.53kg -0.02kg 0.02kg t the test article to the ulcerated oral muco- Appetite t sa.At }0,60,120 an 180 minute increments, " better : 58.2% 60% 60.2% 55.3% ambient and sti~ulated,~pain were recorded [ * stahle/worse 41.8% 40% 39.8% 44.7% by VAS and assessments of percent of remain- Patients evahmble for 3 months ing test article on the mhcosa were made Tot pop Harm Lung OtherHorm and redorded...... (_!~4 )...... :..qe2~'.'..~(~'sL._(.~4)...._...L i,'.~'.'...4d2)...... he improvement in pain with use of the test Prior meanWIoss 4.2kg 3.65kg 4.78kg 4.38kg article had p values~C~OOOl in all time in- Mean Wgain monthl 0.58kg 0.71kg 1.21kg O.06kg Mean Wgain month3 1.2kg 2.2kg : 2.32kg -0.27kg crements compared to baseline values.The &m_ i: ount of test article remaining on the ulcers Appetite (month3) better 62.6% 62.5% 61.8% 63.4% exceeded 70~(on average)at the 180 minute stable/worse 37.4% 37.5% 38.2% 36.6% measurment. Out of study after 2 months 84/304 18/90 34/93 32/121 after 3 months 170/304 42190 59/93 69/121 Conclusions: Farlutal 500rag b.i.d, is active in the cancer anorexia- cachexia sylldrome, apparently independent of the tumour hormone SOMATOSTATIN ANALOG FOR 92 dependency. The effect on bodyweight is correlated with the effect oll INTRACTABLE DIARRHEA FOLLOWING appetite and other subjective parameters. PERCUTANEOUS INFILTRATION OF Randomized trials are warranted to confirm the value of MPA in the SPLANCHNIC PLEXUS FOR PAIN. setting of palliative medicine. &CL.Kurdziel, MD,* C.Duhem, MD, F.Ries, MD, M.Dicato, M D Department of Hematology-Oncology, Centre 4* ROLE OF ~EGESTROL ACETATE IN THE TREATMENT OF Hospitalier de Luxembourg, L- 1210 Luxembourg CACHEXIA IN PATIENTS WITt4 HEAD AND NECK CANCEF~

We report on a 48-year old man with metastatic non small cell lung *Jens B0ntzel, M.D., Klaus KOttner, MD cancer with intractable right lumbar and hypochondrial pain secondary to metastatic infiltration of retroperitoneal tissue and Devision of ENT splanchnic nerves. Percutaneous CT-guided alcoolisation of the Klinikum Suhl/Th0ringen splanchnic nervous plexus was performed. While partially efficient on D 98527 SuN Germany pain, this technique was complicated after a few days by an intractable diarrhea with 10 to 20 watery stools per day resulting in a rapid 8 kg Mortality of 70 % of all patients with tumors in the head and neck is linked with weight loss. Short-term (2-3 weeks) and self-limited modest diarrhea is anorexia and cachexia. Two reasons for cachexia are well known: 1 local disease a classical complication of splanchnic nerve alcoolisation, the underlying mechanism being a paralysis of splanchnic vasomotricity and local therapy preventing oral nutrition. 2. advanced tumors activating causing a malabsorption and a water loss into the intestinal lumen. biochemical pathways of proteolysis, lipolysis and gluconeogenesis. Five groups This was severe and irreversible in our patient. After failure of diverse anti-diarrheic drugs (Ioperamide, diphenoxylate, ...) and of substances are now used to treat tumor-induced cachexia: corticosteroids. dietetary measures, diarrhea was dramatically improved by progestional drugs, cyproheptadine, hydrazine sulfate and anabolic steroids administration of minimal doses of the somatostatin-analog octreotid Between 1992 and 1993 in our hospita} 38 patients with cachexia due to advanced (0,1 mg in a 2 h i.v. infusion pump/3 days). The drug was well tolerated and normal transit was restored. cancers of the head and neck were given 160 mg megestrol acetate per day for Intractable and irreversible diarrhea is a rare complication of 4 month. The increase in body weight was significant after 8 weeks The mean splanchnic nerve alcoolisation in which low dose somatostatin analog increase after full therapy was 4,58 +/- 3,19 kg Treatment of the five woman in the treatment desserves to be tried. series was very successful and all achieved their former body weights Megestrof acetate therapy was best started after assuring enteral nutrition. Significant adverse events were loss of libido for the men, headache and rarely ME,DROXYPROGESTERONE ACETATE thrombophlebitis Our first experiences suggest that megestrol acetate treatment 93* ( MPA ) IN THE TREATMENT OF THE }s useful in cachectic patients w}th advanced squamous cell carcinomas of the CANCER ANOREXIA-CACHEXIA SYNDROME. IS IT RESTRICTED TO head and neck. HORMONE DEPENDENT TUMOURS ONLY ? *J.M. Andrien, C. Focan, Ph. Warnier, L. 95* COMPARATIVE EVALUATION OF Dewilde, P. Van Vliet,H. Wassenaar, J. Van MARKERS OF BONE TURNOVER IN Meerbeeck. ( Belgium ). PATIENTS WITH BREAST CANCER- INDUCED OSTEOLYSIS BEFORE AND Aim of the study :To evaluate the effect ofMPA (Farlutal)500mg b.i.d. AFTER BISPHOSPHONATE THERAPY. on tile evolution of body weight (W), and on appetite and other *J.J. Body, J.C. Dumon, E. Gineyts, P.D. Delmas. subjective parameters in advanced cancer patients. To evaluate whether Rehabilitation & Supp. Care Clinic, Inst. J. Border patient's reaction could be related to the hormone dependency of their ttauour. Brussels, Belgium & INSERM 234, Lyon, France. Patients are treated for 3 months and are evaluable if they are treated for The understanding of the pathophysiology and the monitoring of at least 1 month. metastatic bone disease remain unsatisfactory. We compared 360

several markers of bone turnover in patients with breast As a summary, Polyerga used as supportive treatment had cancer-induced osteolysis before and after a single infusion of the positive effects on some parameter of quality of life in head bisphosphonate pamidronate in order to better delineate the and neck cancer patients during chemotherapy. relative interest of newly developed markers of bone turnover. We studied 19 ambulatory patients with advanced breast cancer and extensive metastatic bone involvement who did not receive any systemic antineoplastic therapy. Patients were treated 7 PE~UTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) consecutively by increasing doses of pamidronate from 30 to 120 IN CANCER PATIENTS: COST-EFFECTIVENESS IN mg and they were followed weekly during a mean of 8 (range 4- 10) weeks. Compared to normal women, 1he percentage of AN ITALIAN HEALTH DISTRICT elevated values was 53% for uCa, 61% for Crosslaps (a new * S. Sartori, L. Trevisani, D. Tassinari, I. ELISA that estimates the level of type I collagen degradation), Nielsen, G. Gilli, A. Maestri 68% for hydroxyproline, and 100% for Pyridinoline (Pyr) and II Divisione Medica e Servizio di Oncologia D-Pyr (collagen cross-links). Pretreatment levels of uCa did not cap. S.Anna, Ferrara, Italy correlate with any of the four markers of bone matrix resorption, whereas the correlations between these four markers Cost analysis of long-term feeding by PEG was done in 34 were all significant (rs=0.64-0.71; P <0.01). Osteocalcin and head and neck cancer patients, evaluating 3 main items. Alk Phos correlated (P <0.05) with hydroxyproline and D-Pyr i) PEG placement, considering gastrostomy kit, consump= (rs=0.50-0.64). Bone resorption markers fell significantly tion variables, gastroscope amortization expenses, pre= after pamidronate therapy, up to d42 for hydroxyproline, D-Pyr and Crosslaps, and d63 for uCa. This longer-lasting effect was medication drugs and staff. 2) Nutrition, considering probably due to the PTH surge following the decrease in serum feeding products, nutrition container and connecting Ca. The fall was the most marked for Crosslaps excretion. In tube. 3) Patient care, dividing the patients into 3 summary, markers of bone matrix resorption were more groups: 17 outpatients, 8 home care patients, 9 outpat= frequently elevated and to a higher degree than uCa or bone 5ents shifting to home care during the follow-up. All formation markers in patients with breast cancer-induced patients had i medical 2 nurse visits/month, plus addi= osteolysis. Due to the PTH surge, the decrease in uCa overestimates the effects of bisphosphonates on bone resorption, tional visits if necessary. The mean daily cost per pat= whereas the marked changes in Crosslaps after therapy suggest lent was calculated adding up the mean daily cost of the that this marker should be investigated for monitoring treatment 3 items, and compared to that of feeding via nasogastric effects on bone in cancer patients. tube, calculated in ii patients using the same criteria. No procedure-related death nor periprocedural complica= tions were observed. 60-day mortality was 3/34. Mean 96* POLYERGA AS SUPPORTIVE THERAPY duration of PEG use was 180.5 days (range 47-6S9). 2 COULD IMPROVE QUALITY OF LIFE IN gastrostomy site infections, treated with systemic an= HEAD AND NECK CANCER PATIENTS DU- tibiotics, were observed during the follow-up. Mean RING CHEMOTHERAPY daily cost of PEG placement, enteral nutrition and pat= E. J. Borghardt~, M.D., B. Rosien*, M.D., S. Frech=, *M. Hartleb~ lent care were Italian Liras (IL) 2,500; 24,510; and ~Deister-SOnteI-Kliniken, Bad M0nder, GERMANY 1,870 respectively (Deutsche Marks (DM) 2.08; 20.4;108] 4HorFerVit Pharma GmbH, Oldenburg, GERMANY for a total mean daily cost per patient of IL 28,880 (DM 24.06), slightly higher than that of nasogastric tube Anti-cancer chemotherapy can often induce a severe reducti- (IL 27,340; DM 22.76). on in quality of life. tn a prospective, randomized double-blind PEG can be considered the procedure of choice for long- study patients suffering from advanced head and neck cancer term enteral feeding of cancer patients also from the were treated with Polyerga, a low molecular weight pepfide economic point of view. preparation, or with placebo during and after finishing chemotherapy (5-FU, platin derivations). The study parameter were lymphocyte counts, quality of life (POMS), Karnofsky performance status, pain, body weight and survival. 8 P~RCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) At the beginning of chemotherapy, Polyerga showed in com- vs NEEDLE CATHETER SURGICAL JEJUNOSTOMY parison to placebo a positive effect on nausea and vomitting. (SJ) IN CANCER PATIENTS During chemotherapy Karnofsky performance status, activity *S. Sartori,M. Baccarini, R. Meloncelli, F. and fatique (POMS) remained stable for Polyerga patients, Pellegrini, R. Cavallini~ Z. Trev~sanJ while the corresponding data of the placebo group worsened. II Divisione Medica e Istituto di Patolo= Furthermore, the body weight was stabilised in the verum group and decreased in the placebo group. gia Chirurgica, Ferrara, Italy. PEG and SJ were compared in a prospective fashion to Pain was reduced during chemotherapy and increased again determine whether one technique was superior in pro= after the chemotherapy was stopped. There was no diffe- riding enteral access for long-term feeding in cancer rence between the two study groups. Polyerga treated pa- patients. 42 patients with head and neck, esophagus or tients showed a tendency to higher T4- and lower T8- cell counts, while placebo patients had contrary data. There was gastric cancer entered the study. 25 underwent PEG and no difference between the two study groups regarding tumor 17 SJ. PEG was placed using the pull-through technique, response and survival. SJ was carried-out according to Delaney's technique. 361

Follow-up was complete to 60 days. No procedure-related 100 PROGNOSTIC FACTORS INFLUENCING 5- death was observed in both groups; 30-day mortality was FLUORURACIL (5FU) INDUCED DIARRHEA 0 inPEG- and 2 in SJ group (both unrelated to procedu= *S.Cascinu, E.Det Ferre, M.Ligi, MBL. Rocchiw re). Mean time to place PEG was ii minutes (range 5-25), G.Ghiandoniw G.Catalano Servizio di Oncologia Medica, Ospedale di Pesaro; to place SJ was 30 minutes (range 18-43). No major and 2 w di Biomatematica, UniversitA di Urbino minor complications were observed in PEG group (2 wound infections, treated with systemic antibiotics); SJ pat= 5FU-related diarrhea is a relatively common problem in the ients had i major complication (jejunal perforation, clinical management of cancer patients. It can reduce patient requiring surgical intervention), 4 minor complications compliance and sometimes it can be a potentially life- (2 wound infections requiring systemic antibiotics and threatening disorder. No prognostic factors influencing 5FU- 2 ileus lasting more than 72 hours) and 2 tube dislodge- induced diarrhea have been identified thus resulting its ments requiring tube replacement. On the whole, com= occurence unforeseable. The aim of this study was to verify if plication rate was 8% in PEG group and 41% in SJ group. some characteristics related to the patients or to chemotherapy (p 0.05). Cost of placement was Italian Liras (IL) and co'.,:!d identify a subset of patients at higher risk of developing Deutsche Marks (DM) 450,000 and 375 for PEG, IL 920,000 diarrhea while receiving a 5FU containing regimen. 154 patients and DM 765 for SJ. (98 males and 56 females) complained of diarrhea grade tI-IV PEG seems to be preferable to SJ in cancer patients,as (NCI common criteria). Median age was 62 years (r. 30-79 both morbidity and cost are lower. SJ should be reser= years). Primary tumors were: colon-rectum 134; stomach 8; ved to patients in whom it is not possible to place pancreas 12. Chemotherapeutic regimens included: 5FU 370 PEG owing to technical problems. mg/m2 iv d 1-5, leucovorin (LV) 200 mg/m2 iv d 1-5, every 3 weeks; 5FU 600 mg/m2 iv weekly, LV 250 mg/m2 iv weekly; 5FU 370 mg/m2 iv d 1-5, LV 200 mg/m2 iv d 1-5, interferon-cz 3MU im d 0-6, every 3 weeks. A logistic regression analysis showed that significant factors related to the occurence of diarrhea were: previous number of chemotherapy cycles (p .0001); previous episodes of diarrhea (p .000i); presence of 99 TP,~rrIc~ ~ DIgraRY ~ (trc~r) primary tumor (p .004); chemotherapeutic regimen FOR 2]NMNAL~ PA1NNIS (5FU/AF/IFN vs 5FU/AF, p .007); season (summer vs others, p Fncr_h Y.L. lai, M.D., Ling~ Yang, Yh.D. .004). Sex, age and the presence of colostomy were not Hospice, Mackay Yemorial Hospital. significant. In conclusion, these results suggest that some Graduate Institute of Hnarmcognosy Science, characteristics can identify patients at higher risk of developing Taipei Medical College. diarrhea during a treatment with a 5FU-containing regimen. Taipei, TAIWAN These factors should be carefully considered before and during One of the end points of hospice movement in Tai~Bn is to create treatment with 5FU. the Chinese model of Im~pice care for our people. ]he trial of TCUr ~as our prefk~ effort for this end point. Sixt~ sequential patients were included in this retrospective study. Questicrmire survey for ~tonemy demonstrated that 60 terminal lO1" DETECTION OF CANCER PATIENTS AT RISK csrmer patients(96.8~o) were positive to take %Cgr. ]hirty-ihree FOR PSYCHOSOCIAL PROBLEMS patients of the W~ gr(xrp were asuned as the control group, * A. van 't Spijker, R.W. Trijsburg, H.L. Van, and 29 patients of the latter group as the test group. Lung CA H.J. Duivenvoorden, T.A.W. Splinter, (27.4%), Breast CA(14.5%), and Breast CA(9.7%) cemprised the ma- H. Verbaarschot-Bockweg, C. Hilvering, G.S. jor distribution of disease entity, ll])T is probed according Kho, H. Tilanus to the priority of their problem lists which ~licated pain(82.8% ), weakness(48.3%), dryness of meuth(27.6%), dyspnea(27.6%) and Dept. Medical Psychology and Psychotherapy, edema(17.2%o). After admission, assessment and regular medication Erasmus University Rotterdam, The Netherlands of pMliative care ~ere performed for 1 week. ~ follwed with tailored menu and served as dessert between m~l~ for another The last decades, it has been shown that about week. ]he results were evaluated by Ferrans' & Powers' method as 20-30% of the cancer patients suffer from psychiatric well as visual analogue rating scale. Main ~ents of menu or psychological problems. Early detection of these were composed of Tremeila fuciformis, Paeonia lactilora & Glycyr- problems is important for effective counseling. rhiza and other traditional nmiicine profounded with vital sub- Research findings showed a relationship between a stance. As the results of evaluation, 24(82.8~) patients ~ows couple of variables (e.g. social support, stage of the their strong affinity to II~. ll~enty-si~(26%) patients felt com- disease) and psychological distress in cancer patients. fortable. Psychospiritual dcemin was significantly favored in However, information on the association between test group. Appetite improvement ~th visual analogue rating personality and psychological distress is lacking. scale also ~nowed impressively better in test group. ]hose having Glycyrrhiza-Paeonia soup revealed ~ relief. No significant In the present study, the relationship between progression in health and function domain could be demonstrated. psychodynamic aspects of personality development It is concluded that %EDT adjuvantly improves quality of life of and the occurrence of psychological distress was the ~ cancer patients. In terms of practical mad clinical explored. extension of II]3T, further Irospective randomized study is Interviews (on education, employment situation, necessary to be organized. relational functioning, and reactions to stressful life 362

events and emotions) were held with 90 patients 103" A R~DOMIZED COMPARATIVE STUDY ON THE suspected of lung or oesophageal cancer (i.e. before IMPACT OF THREE DIFFERENT "PSYCHOTHERA- PEUTIC" APPROACHES INCLUDING PSYCHOSOCIAL diagnosis). Statements of the patients were scored on INTERVENTION ON THE QUALITY OF LIFE OF 8 developmental lines (e.g. social attitude, object- ELDERLY CANCER PATIENTS. relations, coping and defense style) on 3 levels *Giovanni Mantovani 1, Giorgio Astara 1, Biancarosa (immature, neurotic, mature). At baseline and at 3 and Lampis 1, Alessandro Bianchi I, Luigi Curreli I, Walter 6 months after diagnosis, patients filled in self- Orr62, Bemardo Carpiniello2, Mauro Carta 2, Marco reporting questionnaires for depression, anxiety and Sorrentino3 and Nereide Rudas 2 psychological distress. lDepartment of Medical Oncology, 2Department of Psychiatry, Uni- Preliminary analyses indicate that lower levels of versity of Cagliari, 09124 Cagliari. 3Volunteer Association "Project development of social attitude, object-relations, Anthropos", Cagliari, Italy. coping and defense style are positively related to The aim of this study was to assess the impact of three different types of psychological distress. psychologic approaches on the quality of life (QL) of elderly cancer patients with symptoms of anxiety and/or depression and undergoing multidisciplinary antineoplastic therapy. Seventy-four patients aged over 65 years with solid tumors in different sites or hematological malignafi- cies, generally in advanced stages (III-IV), were enrolled in the study, ETHICAL CONSIDERATIONS IN INVOLVING RESIDENTS seventy-two of whom (42 men and 30 women, mean age 70.68, range 102" IN TRUTH DISCLOSURE 66-85) were evaluable. The patients were randomly assigned to one of G. Bennett Humphrey, M.D., Ph.D., *Joy D. Skeel, MDiv., three treatment groups according to the main prognostic factors: Group Mahmoud Hakim, M.D., Donald T. Wasik, M.D. A, psychopharmaeologic treatment; Group B, the same as Group A plus Departments of Pediatrics, Psychiatry, & Medicine "social support carried out by volunteers" and Group C, the same Medical College of Ohio treatment as Group B plus "structured psychotherapy". The evaluation of Toledo, Ohio, USA patients' QL was assessed using either uni- or multi-dimensional instru- ments to explore the functional status and physical symptoms as well as PURPOSE: This research evaluated responses of 2nd year pediatric residents when asked to disclose bad news to children/adolescents the psychological status at different times during the antineoplastic with cancer. Ethical issues were identified and expMred While there treatment. The following points were highlighted by our study: first of are a number of articles discussing disclosure, there is little written on all, the pharmacologic therapy (alprazolam + sulpiride) and other speci- ethical issues in this important and difficult area. The experience of fic ancillary treatments, such as antiemetics, were useful in reducing the residents in leading m discussion with parents of a child with cancer incidence of the main QL-related side effects of antineoplastic therapy, are the focus of this research. such as the anticipatory and post-treatment nausea and emesis. Secondly, DESCRIPTION: Residents: In training at either an academic or private hospital. Patient/parents: From Hematology/Oncology the integrated treatment approach which combined drug therapy with service. Disclosure was the responsibility of the faculty and verbal social support carried out by volunteers with or without structured - permission was requested of the parents before beginning the psychotherapy, significantly improved the QL of elderly cancer patients. disclosure. Model: When a child/parent must be informed of change Finally, our study design did not allow us to decide whether the in prognosis, life-threatening event, need to consider no structured psychotherapy, based on short-term autogenous training, may resuscitation, etc., the 2nd year resident assigned to the case is given the option to disclose the information. For those that accept, there is have potentiated the effectiveness of social support provided by the private discussion between the resident and one faculty (GBH). An trained volunteers: this could only be answered by a design where the example of structured disclosure (preamble, disclosure, two psychosocial modalities would be directly compared. rehabilitation) is reviewed and content of disclosure outlined. The disclosure process is limited to resident, faculty member and parent/chill. After completion of disclosure, the resident's performance was critiqued by faculty member. Assessment: A questionnaire (demographic data and prior experience in disclosure) 104" THE INFLUENCE OF ENVIRONMENT ON was administered and a 30 minute structured confidential interview EMOTIONAL EXPERIENCE AND was conducted by a clinical ethicist (JDS). Attitudes and previous experience varied widely. The aggregate critique was that CONDITION OF CANCER PATIENTS participation in this experience was both very stressful and very * E. Andritsch, I. Kuss, W. Freidl, N. Klackl, J. valuable (ethieist, JDS). Surprisingly, a number of residents were Kreuzer, H. Samonigg excluded from disclosure by some faculty. Disclosing a life- Division of Internal Medicine, Department of threatening event was less of an ethical issue than discussing impending death. Residents did express their concerns about telling Oncology, University Graz, Austria the younger child bad news of any kind. CONCLUSION: Major ethical issues were detected: 1. Lack of Diagnosis of cancer means for the patients a disruption in his guidance for disclosure on non-oncology services; 2. Unwillingness forward life trajectory. A plenty of time the patients spend by some faculty to involve residents; 3. On rare occasions the with medical treatments and the experience of the atmosphere resident was rebuked for revealing information when asked questions by a family member when the responsible faculty was not available. of clinical wards seems sterile and technical for them. This Such ethical issues for residents cannot be addressed or corrected may cause a negative attitude towards the attending without full cooperation of all team members. physicians and can not be promoting for effective coping styles. Itlnes, especially cancer does not only reflect a dysfunction in metabolic pathways but also offers a new chance to mobilize life and the patients inner ecology is thereby changed in a positive way. In this respect the atmosphere during cancer therapy is of major importance and has influence of the perception of the disease itsels Colours play an important role in our every day life - the rooms in 363

which we live, the clothes we wear and the nature which threatening illness. Many parents report the lost sense of unlimited potential. Prolonged treatment, long term recover),, pain, follow-up protocols, all could shows a fascinating variety of colours. We purposely have be also disruptive for the family. The most difficult issue that families must face chosen a provocative creation to change the clinical is the loss of control of their own lives (daily organization, perception of family atmosphere of our ward by inviting the artist Friedensreich unity) and, whatever the outcome, families will experience a great loss. Nevertheless a child death shakes the foundation of a family. Many studies have Hundertwasser. This improvement of a lively surrounding been carried out on quality of life in cancer patients, during ~xeatment or after, but, should minimize most of the stress factors for patients as well what do we know about outcomes when a child dies? In the Oncology Service of as for medical staff. We investigated the influence of the Pediatric Clinic of the University of Rome "La Sapienza" , we evaluated parental occupation and health, offsprings, divorce, pregnancy, volunteer work, environment and emotional experience in cancer patients and forms of charity in two different groups of families with children affected with before and after adapt/on of our oncological ward. From cancer. In the ftrst group the child died of disease (Fl: 46 families), in the second, August 1993 to October 1994 we interviewed a total of 200 instead, sttrvived (F2:34 families). Both them appeared homogeneous for all the variable tested, but only one significant difference (p~0.05, OR = 3.71) was patients with malignant or other diseases. For evaluation we revealed to the number of new pregnancies after death/diagnosis. Nineteen of 36 used standardized as well as individualized questionnaires families (52,7%) evahiable (mathemal age less than 45 yrs) of cluldren dead for Study design and final results will be presented. cancer had a new pregnancies, 13 of these (68,4%) less than one year after the death. In F2 instead, new pregnancies were only g of 33 cases (24,2%). Replacoment child syndrome, which refers to a child who is used as a substitute for a son who has died, could explain this difference. The replacement PSYCHOSOC|AL preparation for bone Marrow child is often e~ed to emulate the idealized image of the dead child and is 105" TRANSPLANTATION (BMT) - preliminary findings thereby not allowed to develop his/her own identity. Replacing a child with from Australian controls with reference to an another allows the parents partially to deny the first child's death, actmg as a intervention focussing on EMPOWERMENT. barrier to parental acknowledgment of death. Parents should be adviced by the *Desmond J. Perry, B.Sc., Dip. Grp. Work. Dip. ReI.Ed., oncologist and/or pediatrician about the danger of having another child before Dip Soc. Sc., B. Soc. Adrnin., M.S.W., resolving their grief. School of Social Work Acknowledgement: This study is supported by CNR ACRO n.94.01110.39 University of New South Wales Sydney, N.S.W., AUSTRALIA.

The medical model has often been accused of disempowering patients - of focusing on the physical symptoms, avoiding other factors which contribute to recovery. There is an increasing Cervical intraepithelia) neoplasja . 107 (CIN): the role or psycnosoc]at rac~ors interest in psychosocial factors in treatment, and on quality of life. This paper draws on clinical experience, and research *Adriaan Visser,PhD, Ad Vingerhoets,PhD, literature in outlining some of the major issues seen as important Karl Goodkin,MD,PhD, Lex Peters,MD,PhD for psychosocial preparation for BMT. An intervention is described aimed at empowering patients to take back some of Helen Dowling Institute for Biopsycho- the control of their own preparation. -social Medicine, Rotterdam, Netherlands Background A five year study funded by the New South Wales State cancer It has been established that high risk human papilloma council is under-way at four hospitals in Australia - Sydney, virus(HPV) types play a role in the promotion of Melbourne, Adelaide and Brisbane. An intervention is being cervical cancer. These HPV infections are associated with decreased immune function. This suggests that the trialled with a group of patients at the Royal North Shore Hospital immune system and related psychosocial factors contri- (Sydney}. Data collected from the control groups is disc..:ssed bute to progression of dysplasia. The aim of a recent- showing factors influencing adjustment post-transplant. ly started study is to prospectively investigate the potential of psychosocial factors to predict the cour- Over 100 patients have been interviewed using both a se of CIN, using a szress coping moael. It is expected that having experienced negatlve and uncontrollable quantitative and qualitative methodology, The research life events, and favoring a more passive coping style instrument includes: perceptions of preparedness for BMT, including denial and re~ression, with inadequate soci- perceptions of difficulties post-BMT, and psychosocial al support is associated with a less favorable outcome adjustment: including anxiety, depression, commitment to 'fight in CIN progression (controlling for gynecological, on', Sense of hopelessness/helplessness, and fatalistic outlook. sociodemographic and life style factors related to CIN and to immune functioning). While the findings are preliminary, there are pointers to what Pilot study may contribute to improved outcomes for bone marrow A pilot study was held at three clinics where women transplant patients: These include age, marital status, were treated with a abnormal Pap smear. The level of employment, income source during BMT, preparedness for BMT, dysp!asia was proved in 26 women. Before the women and perception of difficulties after BMT. The preparation recelvea information on the outcome of the medical test they filled out a questionnaire. The distribution procedures followed in each of the four units are also discussed. of the CIN levels was: No CIN(15%), CINI(31%), CINII(19%), CIN III(19%), missing (13%I, The results indicate that the women wlth a higher CIN level show: a less healthier life style, delay in Pap FAMILY AND PEDIATRIC CANCER: smear check-ups, a passive coping style, a higher 106" The replacement dynamics. number of short lasting life events, and a higher stress level. A.Clerico, G.Ragni*, A.Amimi, A.Minori, G. Varrasso, Conclusions E.Properzi, M.A.Castello. The result confirm the hypothesized psychosocial Oncology Service - Pediatric Clinic, model. A main study among 800 women has been funded by University of Rome "La Sapienza" the Dutch Cancer Society. Also relevant immune mea- sures will be studied. The findings would have poten- Caalcer develops suddenly in a previously healthy child, symptoms are tial relevance for the development of behavioral in- aspeeific, the diagnosis is reached while parents are still unprepared to face a life terventions to prevent CIN and its progression. 364

I ~'~ PSYCOSOCIAL ASPECTS OF INTEGRATED HOME CARE A'Fr'ENDANCE potential problems. Specifically, the life ,~p,v PROGRAMME TO THE ONCOLOGICAL TERMIhIALLY ILL PATIENTS (ADI) of a support group sponsored by the 0] LOCATELU P., (1) FRATUS F, (2} ARNOLDI E. Leukemia Society of America for patients with Leukemia and associated diseases will (I) PSYCOSOCIALSERMCE- {2) MD. MEDICAL ONCOLOGY - USSL 12 be detailed. The group has been in TRESCORE BAL.NEA,qlO- RERGskMO - ITALY existence for eight years and currently has tN THE MONTH OF DECEMRER 1993, THE ADI PROGRAIIIIdE HAS STARTED WITHIN THE FORMER 18 active members. The success of the group USSL 3~J (SERIATE . BG'~. THE GENERAL GOALS OF PSYCOSOCL~ INTERVENTION WITHIN A is rooted in the members willinqness to

DOMICIE.LAI~ ATTENDANCE SERVlC~ TO 0NCOLOGICAI. ILL PATIENTS CAN RE SUMMER UP IN share in their journey through disease together. THE IMPORTANCE OF ESTABILISHINGS AN INTEGRATION BEI~%EEN THE HEALTH AND THE

PSYCOSOCI~ ASPECTS IN THE MANAGEMENT OF file PATIENTS NEED AND THEIR EAIIILIES, IN

ORDER TO RUN " QUAI_ITATI'VELY " USEFUL SEAVtCE IN FAVOUR OF THE TERMIflAI.LY ILL

PATIENT. IN THIS PROSPECTIVE RESIDES THE SANITARY FIGURES OF THE DOCTOR AND

NURSE, THERE IS THE INSERTION IN THE WORKING TEAIII OF THE PSYCOLOGISTAND OF THE

SOCIAL WORKER. DURING THE TE.AM MEETINGS, RESIDES MEDICAL AND NURSING ASPECTS, THE I~LATWES REQUESTS OR NEEDS ORIENT'ED TO A MORE SPECIFICALLYWELFARE AID, ARE 1 1 0 NURSING MANAGEMENT OF PATIENTS TAKEN INTO CONSIDERATION IN TERMS OF DOMESTIC HELP ]BUREAUCRATIE AND SUPPLYING WITH METASTATIC MELANOMA

OF HEALTH AID SUPPORT. FURTHERMORE, THE TF-AM'S GOAL OF IS TO HIGHLIGHT THE TREATED IN A DAY HOSPITAL WITH

PSYCOLOGIC/~ DIMENSION OF THE WHOLE sITUATIoN, AND TO AIC6&ySING IT SO THAT WE CISPLATIN (CDDP), DACARBAZINE

CAN DEDUCE OPERATIVE MOD/U.ITIES MORE S'VlTADLETO THAT SPECIFIC DOMESTIC SYSTEM. (DTIC), INTERLEUKIN (IL-2), AND TAMOXlFEN (TAM). REGINNING 1994 UP TO NOW, PSYCOLOGIST AND SOCIAL WORKER HAVE GOT IN TOUCH WITH H. Limborgh Meyer, L. Belli, R. Negri, C. 91 PATIENTS, 69 OF THEM HAVs BEEN FOLLOWED BY THE SOC1AL WORKER OR BY THE Zanella, A. Augugliaro, G. Passerai, P. Rossi PSYCOLOGIST OR BOTH. THE SOC~L WORKER ~ PERKa~ENTLY FALLOWED 40 PERSONS Day Hospital, Medical Oncology, Santa OUT OF 69 DURING ALL THE TIME THAT THE PATIENT WAS IN OL&NGE OF THE ADI Chiara Hospital, Pisa, Italy. PROGRAMME. MOST OF THE REQUESTS COHCERNED INFORMATION, AID IN GE'TI"ING THROUGH THE INVALIDITY AND GRANT pRACTICES, ARRANGEMENT OF DOMICILIARY The goal of nursing care in this protocol is to improve the

ATEENDANCE SERVICES SUPPLIED BY THE TOWN COUNCIL OR BY TOWN COUNCILS patients' quality of life during this treatment and to reduce the

ASSOCL~TIONS. PSYCOLOGISTDIRECT AOVICES HAVE BEER TOKEN IH CHARGE BY 26 FAIIIILIES time of treatment in the day hospital.

OUT OF riD. THE MORE FREQUENT REASONS FOR GMNG ADVICE MUST BE RECCONECTED TO Treatment: day 1: CDDP 100 mg/m 2 i.v., DTIC 750 mg/m z,

THE DIEFICUI.TIES DE COMMUNICATION W1THIN THE FAMILY SYSTEM, TO THE pHYSICAL AND TAM p.o. After CBC and biochemistry the patients started the treatment according to the following schedule: 5HT antagonist MERITAL EXHAUSTION AND THE WA]RNESS PROBLEMS AND TO THE DIFFICULTY OF ACCEPTIRG infusion (20 rain), hydration with 500 ml normal saline plus THE DEATH OF THE LOVED ONE TO CONCLUDE, EVEN THOUGH THE ACCESS TO SERVICE IS furosemide (30 min), diuresis control (>300 ml), CDDP 50 ADDRESSED TO PEOPLE WHO NOTICED THAT TOO OFTEN THE PATIENT AND HIS FbJIIILYARE rag/100 ml normal saline (45 min), hydratation 1500 ml (2 h), SEGNALATE WHEN THE PSYCO~HtSYCAL CONDITION ARE ALREADY VERY COMPROMISED, DTIC in 500 ml normal saline (1 h), 5HT antagonist infusion PREVENTING TO PSYCO SOCIAL OPERATORS, WHO NEED MORE TIME TO MEDICJ~-NURSING (30 min). The time necessary to complete the treatment and to FIGURES IN ]'HEIR OPEHATIVE MODALITIES, TO PROVIDE AN AFFECTIVE AND CONCRETE educate the patients is about 5 h. During the treatment the nurses SUPPORT. THE WORK THAT PSYCOLOGIST AND SOCIAL WORKER INDIRECTLY CARRY OUT give the patients information about the sequence and duration of OVER THE PATIENT AKD HIS EAKIILY, INSIDE OF THE TEAM MEETINGS THROUGH THE treatment -- reasons for antiemetic, diuretics and hydratation -- COMPARISON WITH THE PROEESSIONAL NURSES WHO ENTER THE DOMICILE MORE OFTEN and education and dietary advice before, during and after AND CONTINUATIVELYSEEMS TO BE MORE AFFECTIVE OVER THE WHOLE RECORD OF CASES. treatment. Moreover, the nurses educate the patients for home care in the use of antiemetic drugs p.o., dietary advice, anticipation of side effects (fatigue, nausea and vomiting, danger of infection and bleeding, alopecia, mucositis), check for 100 SUPPORTGROUPS in Chronic Illness the correct TAM schedule and side effects. From day 12 to day Cheryl Ann Lane, RN, HA 23 the patients receive IL-2 and the nurses control the blood 1257 Florida Ave. pressure and the premedication with aspirin, indomethacin and Rockledge, FL U.S.A. torecan before IL-2 administration; after IL-2 the nurses check the blood pressure and give information on side effects (fever, myalgia, hypotension, nausea and vomiting, diarrhea, Support groups within health care date back sleeplessness, chills, itching). With this intense nurse--patient to 1905. The diagnosis of a chronic or life relationship we have achieved the following results: (1) The threatening disease creates a situation waiting time before IL-2 administration was reduced. (2) The severe enough to disrupt an individuals side effects of IL-2 were significantly reduced, because of better usual coding patterns. The literature management. (3) The information collected from the patients supports the concept that a person's support became more detailed and precise as we went on with this system can be a significent determining factor in how the crisis is handled. This treatment. We feel that a good nurse--patient relationship can paper will discuss the types and the role improve the wellbeing of the patients during this toxic of support groups, their benefits and treatment. 365

IMPROVING PSYCHO,SOCIAL SUPPORT FOR Adjustment to Illness Scalo (?.\iS), either in the 111 BREAST-CANCER PATIENTS BY MEANS OF health care setting or by mail. It is anticipated A MULTIDISCIPLINARY CARE-PROTOCOL that at least seventy-five subjects will have completed the three data collection periods and *A.van Wersch PhD, J. Bonnema MD, A. van Geel PhD, B. Prinsen MEd,J. Pruyn these data analyzed by the time of the presentation. PhD,E. Taselaar, Th. Wlggers PhD The objectives of data analysis are I) to examine Dr. Daniel den Hoed Cancer Clinic, Institute the overall relationship between subjects capacity of Health-and Environmental Issues. Netherlands to cope and adjustment to illness and 2) to compare Institute for Care and Welfare. Netherlands Organisation the pattern of subjects' adjustment at 6 & 12 months. for Breast-cancer Support-groups Multiple regression and repeated measures ANOVA will Rotterdam, the Netherlands be used to determine whether subjects with high scores on the life scale will achieve scores on PA!5. The literature Indicates that the psycho-social support of cancer-patients might be significantly enhanced by Improvements in Information-flow: both between care- 1 13" INTERNATIONAL INQUIRY ABOUT professionals and patients, and between the various care- INTENSIVE CARE INANTICANCER professionals themselves. For example, patients find It CENTERS. difficult to ask approprate questions, to elicit the * Jean-Paul Sculler, M.D. and Evelyne Information they desire; and professionals may know little Markiewicz, R.N. about the care, lnfornaatlon and support provided by Department of Medicine. colleagues. Institut Jules Bordet, Universit6 Libre de A national Inventory of existing protocols, as well as Bruxelles, Brussels, Belgium. extensive preliminary interviews in Rotterdam, revealed the Intensive care is more and more often used in the management of absence of an integrated and patient-oriented approach. cancer patients. In order to determine if and how critical care Accordingly, a multidisclplinary care-protocol was facilities can be used specifically for these patients, we performed developed, which comprehensively describes, in 15 stages. the process and modes of treatment of breast-cancer a world-wide inquiry in anticancer centers selecting the hospitals. patients. In the context of psycho-social support, It We mailed a questionnaire to 146 centers and we received 84 includes attention to the help which patients should responses (57.5 %). There was at least one oncological (i.e. with receive following the 'bad news', and to facilitating their > 50 % of cancer patients) ICU in 59 (70 %). The majority of the contact with fellow-sufferers. ICU were found in the European institutions (30/59). Of the 40 To date, 53 patients and 81 professionals (e.g. specialists. Occidental ICU, the main characteristics were the followings : laboratory staff, and nurses both inside and outside the type of ICU general suruieal medical hospltall have participated in use and evaluation of the n 17 14 9 protocol. For the most part, it has been positively Median number of beds 8 7 7 evaluated, by both care-professionals and patients. Both (range) (4-18) (t-22) (1-15) groups report that working with the protocol leads to an improvement in information-flow and to more psycho- Medical director speciality anesthesist anesthesist medical social support being given to patients. oncologist Chief nurse qualified : - in critical care 12 9 8 - in oncology 6 5 7 Median RN number per bed 2.5 2.5 2.0 PREDICTION OF COPING EFFICACY 112 Critical care technics used : *Anne Belcher, RN, PhD, FAAN, mechanical ventilation 17 13 6 Mei Ling Yeh, RN, MS hemodynamic monitoring 17 12 8 University of Maryland School of hemodialysis 6 5 4 Nursing Baltimore, Maryland USA In conclusion, ICU appears to be available in the majority of anticancer centers and are often managed by physicians and The purpose of this study vlas to identify predictors nurses qualified in both intensive care and oncology. These data of successful coping in persons with cancer. It was postulated that if such predictors could be suggest that oncological intensive care should be part of training of oncologists. identified at an initial assessment early in the patient's disease trajectory, the health care provider could then facilitate the adjustment of those persons who need assistance in the selection 114" uSING PREDICTIVE INFORMATION IN and use of effective coping skills. It is known DECISION MAKING FOR TERMINALLY ILL that the selection and use of effective coping CANCER PATIENTS. *Charles Martin, Ph.D., skills is likely to improve the patient's quality of Carmen Escalante, M.D., Scott B. Cantor, Ph.D., Linda life and may positively affect response to the S. Elting, Dr.P.H, and Edward B Rubenstein, M.D. disease and its treatment. Patients with lymphoma, Ambulatory and Supportive Care Oncology Research breast cancer, cervical cancer and prostate cancer Program. The University of Texas M. D. Anderson aged 20 to 70 ~Jho were four to six weeks post Cancer Center, Houston, TX, USA diagnosis ~sere asked to participate in the study. Purpose: Prognostic models have been developed that predict imminent Those who signed the consent form were asked to death (survival less than 2 weeks), survival less than six months, and complete a demographic data form and an instrument survival longer than one year in patients presenting to the emergency v~hich measures one's views on dealing with life's department (IED) with acute dyspnea. This study addresses physician daily tribulations, the modified Sense of Coherence utilization of prognostic information, their preferences for additional Scale (called the Personal View of Life Scale information, and the presentation of this information to physician, patient, At the end of six and t~-~elve months each subject was and family decision makers in the most sensitive, useful, and ethical asked to complete the Derog~tis Psychosocial manner. 366

Summary: Triage vital signs (respiration and pulse), history of metastatic 1 1 6 PREDICTING DEATH IN LUNG CANCER disease, and b'Pe of cancer (lung, breast or other) were predictive of survival OUTPATIENTS PRESENTING WITH in a derivation set of 122 acutely dyspneic pts. If these results are ACUTE DYSPNEA. *CP Escatante, MD, L Elting, confirmed in the validation study, data-based recommendations can be DrPH, C Martin, PhD, SB Cantor, PhD, T Harle, made for inpatient and outpatient hospice care or for further therapy in this MD, E Manzullo, MD, K Price, MD, S Kish, RN, EB patient population. Results of the prediction study are presented as a Rubenstein, MD. Ambulatory and Supportive Care prognostic model (odds ratios and confidence interv-als), a decision analysis Oncology Research Program. U.T.M.D. Anderson model (decision tree), and as survival curves. With the overall goals of Cancer Center, Houston, TX, USA. communicating this information to patients and making the most Background: Dyspnea is a common problem encountered by many cancer appropriate referral decisions, ED physicians and oncologists were asked patients and it is the fourth most common complaint of patients presenting how they would use the prognostic conclusions, their preferences for to the emergency department (ED) at Thc University of Texas MD additional information, and how best to present the information to enhance Anderson Cancer Center (UTMDACC). Lung cancer is the most common physician-to-physician and physician-to-patient/family decision maker malignant- in these patients. Our objectives are to describe these lung communication. Preferred methods of presentation, situations requiring cancer patients and to determine factors that predict their death during the further data and ethical dilemmas will be described. first year following initial presentation to the ED with dyspnea. Patients and Methods: Between January 1988 through December 1990 Conclusions: Prognostic information can be useful ill making over 1000 consecutive patients presented to our ED with dyspnea. Of those, recommendations for hospice care, palliative care, or further antineoplastic 321 were lung cancer patients. We chose a random sample of 45 patients treatment. Quantification of the information, confidence in the findings, for further study. Of those, the median age was 58 years and 34 (76%) were and presentation to decision makers will affect its usefulness in improving male. The majority, 62%, had a history of metastatic disease, 30% local, patient care decisions. Further research is needed with patients to assess and 7% no evidence of disease. At the time of presentation 82% had their preferences for prognostic information and how to best present uncontrollcd, progressive disease. Prior to their ED visit virtually all findings in a meaningful and ethical manner. patients (89%) had received cancer treatment. Results: The most common causes ofdyspnea ~re: primary lung cancer (67%) COPD (27%), and pneumonia (9%). 36% ofpatients received antineoplastic treatment following their ED visit. 28 patients (62%) were admitted to the hospital from the ED for further management of their dyspnea, and the median length of stay was 8 days (range 1-101 days). 15 115 APPLICABILITY OF SEVERITY OF ILLNESS MODELS FOR (56%) died in the hospital during their initial hospitalization. The median CANCER PATIENTS: *Jeffrey S. Groeger, MD 1, Stanley survival following the ED visit for dyspnea was 4 weeks (range 0-229). The Lemeshow, Ph.D., David Nierman, MD 2, Kristen Price, MD3, mortality rate was: 32% at 2 weeks, 77% at 3 months, 89% at 6 months, David Horak, MD 4. Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY, USA. and 93% at I year. By using x 2 statistics and logistic regression analysis, the follmving factors were determined to be most successful predicting survival in this group: triage respiration rate >26/rain. and CXR findings Introduction: A severity of illness tool is required in order to compare of loss of lung volume, interstitial edema, and heart enlargement (p<0.05). outcomes of critically ill cancer patients requiring Intensive Care Unit (ICU) management, Before evolving new models we wish to evaluate existing Conclusions: Survival of lung cancer patients after presenting with an models for their application in this population. initial complaint of dyspnea to the ED may be predicted by the triage Methods: Beginning July, 1994, all patients with cancer admitted to the respiration rate >26/rain. and CXR findings of loss of lung volume, Med/Surg ICU at MSKCC ~, and all medical or emergency surgery patients interstitial edema, and heart enlargement. If these results are confirmed in admitted to the ICU at Mount Sinai Medical Center 2, New York, NY, MD a prospective validation study, lung cancer patients with predicted mortality Anderson Cancer Center 3, Houston, TX and, City of Hope National Medical Center4, Duarte, CA, are being followed prospectively to describe the efficacy less than 6 months may be appropriate for hospice referral. and outcome of their ICU care. Mortality Probability Model II (MPM) and Simplified Acute Physiology Scores II (SAPS) scores were calculated to determine probabilities of mortality. All data is presented as mean _+s.d.

Results: The study population consists of 805 consecutive patients, aged 117 Management and treatment of CARDIAC 60 -+ 1 6 years (range 18-90.2), TAMPONADE and RECURRENT PERICARDIAL All Solid Leukemia Lymphoma BMT EFFUSION in the course of malignancy patients Tumor Myeloma IWitold Tomkowskl Ph.D, Monika Szturmowlcz Ph.D., Janusz No. 805 443 221 141 119 Patients Burakowskl M.D., Anna Fijatkowska Ph.D., Stanislaw Filipecki Prof. Mortality .41 .32 .61 .42 .56 Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. MPM .22 • .21 .25 • .22 .18• .17• .16• ROC t .625 .656 .635 .626 .583

No. 24hr 658 359 186 113 101 In 40 cases (mean age 54 years) with large malignant Mortality .42 ,32 .61 .42 .57 perlcardial effusion and/or cardiac tamponade pericardiocentesis under 2D echocardiography was MPM 2,~, .20 + .21 .23+.21 .19• .14• .16• performed. No complications after mentioned ROC .673 .693 .773 .652 .662 procedure were observed. Pericardiocentesis was SAPS .23 • .24 .17 • .20 .35 • .24 • .28+.23 followed by catheterization of perlcardlal space ROC .776 .724 .798 .727 .770 with thin polyurethan catheter. Mean period of The -values for the fit of all models are <0.001. * ROC-Receiver operating perlcardial catheterization was 12.5 days ( range chan ~cteristic curve. BMT .. Bone Marrow Transplant 1-64). In 4 cases bacterial pericarditis during Conclusions: While MPM II and SAPS II provide reliable estimates of hospital catheterization was observed. Mean volume of outcome for a general ICU population, they do not provide reliable estimates of outcome for critically ill patients with cancer. Either customization of the perlcardial drainage was 2.41 (range 0.4-131). 25 existing systems with subsequent validation or development of a new severity cases of malignant pericardial effusion were treated system is required for critically ill cancer patients. with direct pericardial administration of cisplatin, 367

3 with 5 FU and 2 with administration of ed that between 50 and 70 pegcent of these tetracycline. Good results (no fluid reaccumulation) p;~tients experience distressing respiratory were observed only after cisplatin therapy in 22 symptoms st some time during the last six cases - 88~ good results in cisplatin therapy group weeks of life. (20 mg of cisplatin in 20 ml of normal saline was Dyspnea in the terminalphase of an illness instilled over 5 minutes on 5 consecutive days has always been a very difficult s?~optom directly into pericardial space). No local, to manage ~nd,to date there has not been hematologic, renal and cardiac complications after any recommended standardized palliative ap- cisplatin therapy were observed No signs of proach.Opioids,although mot in general use constrictive pericarditis were documented in long for the management of dyspnea,have been ad- lasting responses. We conclude that mistrated through a variety of routes,and perlcardiocentesis performed under 2D available evidence supports the contention echocardiography, followed by pericardial that they do nrovide effective and reliable catheterization and direct pericardial treatment relief,The nebulized route has been found with cisplatin are methods of choice in cases with to be effective in patients with chronic cardiac tamponede and recurrent malignant obstructive pulmonary disease. pericardial effusion. The following ten cases studies il~ustrate the use of this treatment modality for dys- pnea and cough in patients in their owo CY'I'OPROTECTIVE EFFECT OF INOSINE homes. 118 ]IN PERIPBERAL BLOOD I,YMPIlOCYTES Our experience to date indicates'that tre- DURING EXTENDED RADIOTHERAPY OF atment of dyspnea with nebulized opioids is PATIFaTS WITH IIODGKIN'S DISEASE an easy,safe and effective means of reliev- ing this distressing s~ptom in patients b.Y.Koritova., N.V. IIyin., with malignant disease. Because of these fac- C.N.Kolubaeva., N.A. Abissova., tors,the methodology has demonstrated that C.F.Vershinina., L.P. Vaz'temyan., its use can permit patients themselves to V.E. Komar. control symptoms effectively and to thus ~e- CenCral Research Institute of Radio- main at home for most-if not all-of the ter- logy, St.-Petersburg , Russia. minal phase of their illness.

I8 primary patients with Hodgkin's disease were treated with a extended radiotherapy-mantle, Y-in- 120 ECONOMIC ANALYSIS OF PHOTODYNAMIC verted nodal fields subtotal body irradiatlon-at THERAPY VERSUS ND:YAG LASER the I5 MeV linear accelerator utilizing total dose THERMAL ABLATION THERAPY FOR PARTIALLY OBSTRUCTING ESOPHAGEAL 40-It4 Gy at the fiest step of ~ultitumour therapy. CARCINOMA IO patients were given the Inosine every day I20Org *G. Dranitsaris, M.Sc.Phm., M. Siemans, R.N., during radiotherapy. 8 patients have bee,1 the con-- and D. Schneider, M.D. Pharmacoeconomics trol group, without Inosine. The cor~side1"able decre- Research Unit, Ontario Cancer Institute/Princess Margaret Hospital, Division of Gastroenterology, ase (up io 70,5~) o[" the number of peripheral blood The Wellesley Hospital, Toronto, Canada. lymphocytes with mieronuelei was established in patients of the Inosine group as comp:Jrcd to the Cancer of the esophagus is a malignancy with significant mortality and morbidity where patients usually present with dysphagia and nlmlber of lymphoeytes of the control group. nutritional deficiencies. Photodynamic laser therapy (PDT) is an Conclusion: Inosine is the active radioeytoprotecti- investigational treatment designed to correct the dysphagia and enhance quality of life. In this report, an economic analysis of PDT ve agent in the peripheral blood lymphoeytes at relative to Nd:YAG (neodymium yttrium-aluminium garnet) laser prinmmy patients with Hodgkin's disease during thermal ablation therapy in patients with partially obstructing esophageal carcinoma is presented from the Canadian and United extended radiotherapy. States health care environments. This study utilized the clinical trial database from a randomized multicentre phase III comparative trial which determined that PDT and 119 N]~BULIZED OPIOIDS FOR TR~i;ATM2i~T Nd:YAG laser had similar efficacy in the palliation of patients with OF DYSPNEA IN PATiE~TS WITH MIL- partially obstructing esophageal cancer. Patient records were IGN~NT DISEASE examined for information containing hospital resource consumption. MiodragbJeki6,M.D., An economic analysis was then performed from a hospital perspective. Surgical Service,Clinical Hospi- tal'~ntre,Zemun-Belgrade,YU This included the cost of prophylactic medication, endoscopy, laser treatment, tumour debulking, side effects management and all related physician fees. Shortness of breath is an extremely distre- The outcomes from the Canadian hospital setting revealed that ssing and prevalent symptom in patients patients randomized to receive PDT were about $U.S.2787 • 374 with terminal cancer.Studies have determin- (95% CI of the difference) more costly to treat than those in the 368

Nd:YAG laser group. From the U.S. hospital perspective, PDT corrlpared to 32% in adenocarcinoma and 24% in small cell recipients were approximately $U.S.2024 • 982 more costly to lung cancer. Deep venous thrombosis of lower extremities manage than patients who received Nd:YAG. was the source of thrombotic material in 11/33~ only and The results of the current study suggest that in both Canada and vena caval superior, inferior and heart cavities in single cases. the U.S., Nd:YAG laser therapy is a less expensive treatment option In 11/33%/cases pulmonary thrombosis in situ was found. PE than PDT for the palliation of patients with esophageal cancer. was the main cause of death in 29/26%/cases. We conclude that PE is a frequent and dangerous complication of lung cancer. The difficulties in diagnosis of PE in that group of OUTCOME OF PATIENTS WITH IRRADIATED PTS and the prophylactic methods have been discussed. 121 BRAIN METASTASES

*F. Jacob, M.D., D. Devriendt, M.D., M. Paesraans, M.Se., P. Van Houtte, M.D. 123 NEUROPSYCHOLOGICAL ASSES- Institut Jules Bordet - U.L.B. SMENT IN CHILHOOD ACUTE 1000 Brussels, Belgium LEUKEMIA AFTER THE THERAPY *Tomislav Franjo Hajn~id, M.D., Ljerka Brain metastases are dramatic and frequent events during the natural history Cvitanovir-Sojat, M,I)., Vladimir Jugovir, of most common tumor types. We retrospectively analyzed the survival duration of 307 (135 F, 172 M) M.D, Ivica Hajn~i6, M.D. consecutive patients aged 17 to 86 years (mean 56 years; stddev. 12.4) Department of Pediatrics, University with cerebral or cerebellar secondary lesions of various tumoral origins Hospital "Sestre milosrdnice" (164 lung, 63 breast, 24 melanoma, 56 others). All the patients received Zagreb, Croatia holocranial radiotherapy (RT) (30 Gray given through 10 sessions in 2 weeks) and corticotherapy (e.g. Dexamethasone 16 mg/d). Those with The central nervous sistem (CNS) treatment in acute unique operable metastases (17%) underwent ablative surgery. Sixteen % of our patients were given antiepileptic treatment and 46% received childhood leukemia (AL) may consist of either radiation plus chemotherapy after RT. From the 259 patients presenting with neurological chemotherapy (CT) or CT alone. Although CNS therapy symptoms 64% experienced rapid improvement after RT. prevents CNS AL and promotes longterm remission, damage Overall median survival time was 22 weeks (w) (confidence interval : 17 - to the CNS may result in late undesirable sequelae. 26) after the diagnosis of brain metastases. Nor the patients gender, the PATIENTS AND METHODS. Thirty patients (pts) between tumor type, the number and the localization of secondary lesions, neither 2 and 15 years of age were examined between 2 years and up the presence of neurological signs at presentation were correlated to to 10 years after CNS treatment. In AL-pts in remission were outcome. Age might influence the survival as patients younger than 60 studied for developmental, intellectual status and years tended to survive longer than older ones (29 w and 18 w median neurological involvement. RESULTS. We have determined survival respectively; p=0.12). Variables related to a better outcome were the absence of extraeerebral significant neurological, congnition and perception motoric metas"rases and the possibility of neurosurgical treatment. Patients with damages in 16 (53,3%) pts between 2 and up to 4 years aftcr exclusive brain metastases survived 44 w ((2I : 30 - 54 w) compared to 18 treatment and in 10 (33,3%) children after 4-10 years w (CI : 14 - 22) for those with other sites involvement (p--0.005). continuous remission. Electroenccphalographical abnorma- Patients undergoing surgical resection survived 48 w (CI : 35 - 71 w) while lities were detected in 17 (56,7%) pts between 2-4 years and the others survived 18 w ((2I : 14 - 22) (p < 0.0001). in 9 (30%) children between 4-10 years after CNS treatment. We conclude that although a majority of patients experiences improvement CONCLUSIONS. With the great advances made in the of their neurological signs after RT, the overall survival remains poor, prognosis of AL pts much more attention has been focused especially when metastatic disease is not limited to the brain. on the quality of their survival. This must include the detection and the treatment of undesirable sequelae to the treatment of AL. 122 PULMONARY EMBOLISM AS A COMPLICATION OF LUNG CANCER. PULSED ELECTROMAGNETIC FIELD 124 (PEMF) THERAPY OF IRRADIATION * A.FIJAIKOWSKA, B. VERTUN, W. TOMKOWSKI, INJURY D.SZYMANSKA, S.FILIPECKI. B Kragelj, MD INSTITUTE OF TUBERCULOSIS AND LUNG Institute of oncology, Ljubljana, Slovenia DISEASES, WARSAW, POLAND.

Thrombotic episodes have been described in association On the basis of well known clinical effects of PEMF including with a wide variety of malignant tumors. The aim of the study disorders of the musculosceletal system, along with the increasing evidence on the beneficial effects of PEMF on soft tissue and wound was to determine the frequency of pulmonary embolism /PE/ healing, we tried to elucidate the possible influence of PEMF on in lung cancer patients. We analysed 110 autopsy cases of acute and chronic postirradiation injury. primary/79/and metastatic/31/lung cancer/47 women and Twenty-three patients with symptoms of either acute (17 pts) or 63 men- mean age 58 years/. IN 34 cases /31%/ PE was chronic (6 pts) irradiation injury after pelvic radiotherpy were found: in 30/88%/thrombotic and in 4 /12%/tumor emboli. exposed to pulsed magnetic fields (1,5 roT, 45 Hz) for 30 minutes In sqamous cell lung cancer the frequency of PE was 50% daily, through 5 to 17 consecutive days. The objectives of the study 369

were the quality of life, symptoms of irradiation cystitis, bowel injury anthracycline cardiotoxicity. The cardiotoxic effect may occur during treatment or and lymphedema. years liter. Several approaches to reduce anthracycline cardiotoxicity have beea A marked reduction in the severity of symptoms and improved life studied (the use of prolonged or continuous infusion, vitamin E, N-acetylcysteine), but none of these :.have had a positive impact on clinical practice. ICRF-I87 was quality were observed in 11/23 pts - in 8/17 with acute and in 3/6 pts tested in animal studies and was administered in a clinical trial in adult patients with chronic irradiation injuries. No response was noted in 8/ 23 with breast cancer. ICRF-187 seems to have provided effective cardioprotection patients, while moderate regression of symptom severity though without diminishing the anthracycline cytotoxic activity. As of June 1992, !CRF- without any change in the pts' general condition was noted in the 187 was administered to 15 children with solid tumors treated, after diagnosis, remaining (4/23 pts). with different regimens that included doxoru~cin, daunomyein or epirubicin. The Our results suggests that at least in some patients PEMF produce ICRF-I87 was given intravenously 30 minutes prior to the antineoplustic drug; no to.,dc effect was registered. The doxo/ICRF-187 dose-ratio was I:10 while the a significant clinical benefit despite difficulties in objectivization of epiflCRF-187 doseratio was 1:5. Electrocardiographic and echocardiographie symptoms and uncertainties as to the optimal combination of PEMF examinations were carried out both before and after chemotherapy. LVEF, LVFS, parameters and treatment time. EDLV, and ESLV were meamtred with M and B mode echoeardiegraphy. The patients received the following cumulative doses: average dose of r 280 rag/m2, average dose of doxombicin 300 rag/m2, average dose of dannomyein 480 rag/m2. None of these received radiotherapy to the mediastinum. None of these 125 Oncologic Intensive Care Unit: creation patients showed ECG changes or echocardiographicabnormalities. Four patients of nursing-ch~t:integrated with the dai- died of progressive disease. At present, the others are undergoing cardiologic control. A second group of 15 patients (affected with ALL and solid tumors) ly clinical chart received similar doses of anthrecycline chemotherapy without ICRF-187; these *E. Santarossa, L. Roveredo,F.Sian, C. alse underwent ECG and M and B mode echocardiography both before and after Del Pup. Nurses PTactitiones Intensive chemotherapy. None of these received radiotherapy to the mediastinum. In these patients EDLV was increased in 9 cases, ESLV was increased in 6 cases, and Care Unlt FSLV and FE were decreased in 2 cases. The ECGs in all cases showed T-wave Aviano Cancer Center Italy alterations. Although both groups of patients were Iranted with low-doses of The Intensive Care Unit 0CU) at the Aviano Cancer Institute ~as founded anthraeycline, the patients without cardiopmtection with ICRF-187 seemed to in 1992 x~ith a sufficient number of nurses to permit kigh-qualits' objective- demonstrate a worse clinical course and greater cardiotoxicily than those l~eated orientated nursing care (nurse: patient ratio = 1:21. A close collaboration with ICRFtg7. However, longer follow-ups are necessa~ to confirm the between the medical and nursing staff facilitated the introduction of new cardioprotective effectiveness of ICRF-187. operative instmmeots (nursing protocols and procedures) and it ~s also Acknowledgement: This study is supported by CNR ACRO u.94.01 t 10.39 decided to create a nursing chart which could be integrated with the regular daily clinical charL The main objr to improve the quality of care given to the patient in term of efficacy and efficiency. EPIRUBICIN CARDIOTOXICITY : A STUDY The chart is a double-sides sheet. On the front page are the following: 127" COMPARING LOW VERSUS HIGH DOSE 1)patient's personal details; 2)vital parameters; 3)ventilation modalities and INTENSITY PER WEEK SCHEDULES respiratory parameters: 4)fluid and electrolyte balance assessment; 5) drug *C.Duhem, G.Berchem, F.Ries, M.Dicato, administration and diagnostic procedures performed (co-signed by doctor Department of Hematolog~--Oncology, Centre and nurse): 6)laboratory results. On the back page space is allotted for: Hospitalier de Luxembourg, L - 1210 1)nursing interventions performed during each shift; 2) equipment checklist LUXEMBOURG to be performed at the beginning of each shift; 3)summax3, of all equipment in use e.g. drains, venous access sites; 4)list of all procedures performed on Epirubicin is one of the less cardiutoxic alternatives to doxoruhicin. the patients each da3~ 5)space for various annotations. This second page is We studied the toxic effect of total cumulatise dose, and of low versus compiled using a set of com,entional symbols in order to save time. The high dose intensity per week schedules. Sixty four patients were remainder of the sheet is used for assessment of the patient's condition, treated with different epirubicin containing regimens. We confirm the s3~em by system, using a checklist. At the and of each shift the nurse, classical notion that total cumulative doses of less thant 600 rag/m2 do referring to a table describing normal parameters, assesses the patient's not induce significant cardiotoxicity, whereas doses above 600 rag/m2 psycho-physical condition, either describing alterations or conferming a are associated with a trend towards cardiotoxicity. High dose intensity normal situation using one of the com'emional s3anbols. per week patients (> 40 mg/m2) however did have a significantly We have concluded that the advantages of this nursing chart include: lower incidence of cardiotoxicity than the low dose intensity per week I. easy compilation; (< 40 rag/m2) group (22,8 % vs. 50%; p< 0.t15). We identified the 2. immediate comprehension; association of a dose intensity of more than 40 mg/m2/week and a 3. time-saving; cumulative dose of 400 to 899 rag/m2 or a dose intensity of less that 40 4. elimination of errors in transcribing information; mg/m2/week and a cumulative dose uf less than 400. to have the Io~est 5. gives a complete x4sion of the patient's clinical condition and aids the incidence rate of cardiotoxicity. We confirm our previous study that integration of medical and nursing care; epirubicin in high dose intensity per week schedules is not more 6. it is clear and concise and therefore a valuable medico-legal document; cardiotoxic than in low intensiD per week schedules for the same 7 the data collected can be used for research and study purposes in the amount of total dose given. future.

128" Ttt~ USE Olg CARDIOXANE IN CHI~,MOTHERAPY CARDIOToXICITY IN CHILDREN: OF AC'TVI'E LEUKAEMIAS IN CHILDREN 126" PRELIMINARY RESULTS Teresa Jackowska M.D., Marek Pleakot M.D., Rortm Roki,.~ka- Milew~ka M.D.PED; Maria Wrbblewska - Kalmtew~ka MD. Pb_D Sehiavetti A., Colloddi V., Ragni G., Clerice A. Department of Pediatric Haematology/Ontology, Bartolozzi S. and Castello M.A. Depmlnmnt of Pediatric Cardiology Department of PediaWics, University "La Sapienza", Rome Medical Academy in Wangaw, Poland.

Anthracycline antibiotics are among the most effective antineoplastic agents, with Cardioprotection h~ been made with the use of Cardioxane in 22 activity in a wide range of pediatric tumors. The most important doselimiling children ta-e~ed for acute leukemin~. The age of children at diagnosis varied form factor is a dose-dependent irreversible cardiomyopathy. Furthermore, their use can I to 15.5 yem~. be associated with non-specific, asymptomatic electrocardiographic and Anthraeycline~ were applied at a do~e from 150 to 360 rag/m2, echocardiographic alterations. In particular, children appear to be susceptible to Cardioxane I: 15 or 1:20 of the mathraeycline~ dose. No significantchmage~ in the 370

eatdiovagcular gyrtera in the physical r have been observed in may of to prevent the acute, 5-FU-induced gastroduodenal muco= the dill&era In the ECG evaluntion four children were found to have sal injury. The efficacy of Ranitidine is questionable, tupraventrienl~ tad~csrdia, ST ~egnmat depresgion was detemfined in two owing to its weaker and shorter antisecretory activity. children and e..m'iysign~ of left ventricle (LV) sb-oin in one child. ECHO hag been performed bd'orr during as well as one month mad 6 mota~ rafter the trenlment Before the application of em-dioprotectionthe size of the LV in di~tole ROLE OF LIPOSOMAL ENCAPSULATION OF (LVIDd) wtd s"~ole (LVIDs) w~ nom'ml. %EF varied in all children from 49 to 130 DAUNORUBICIN TO REDUCE CARDIOTOXICITY : 83% (mean 64 %EF in children lrented with anthracyclines without STUDIES WITH ISOLATED PERFUSED RAT HEARTS. e~rdioproteaion wag low~ that in children who had not been trented with P. Pouna t, S. Bonoron-Ad61e2, L. Tariosse 2. P. ~rdln-~-'yelines mad wag 5'7.3% trod 68% respectively %8F vnried in the whole Besse 2, and J. Robert 1. (1)Institut Bergoni6, group from 23 to 50% (mean 34.9%) mad the mean vnlues in children tre_nted Bordeaux ; (2) INSERM Unit6 8, Pessac, France with nnthracyelineswere lower thnn these in children who had not been trented with mlahracyclinesmad were 30 trod 37% respectively. DaunoXome is a liposomal formulation of daunorubicin presently under During the Cardioxane application increase in the diastolic gize of the evaluation. In order to evaluate comparatively the effect of daunoXome lett ve~icular has been observed, wherea~ the systolic size did not ~how at~ and free daunorubicin on the contractility and relaxation parameters of dgnificant changes when compared with values before the treatmeaL Impairment cardiac muscle, we have used isolated rat hearts preparedaccording to of contraction activity of the leR ve~ri~lm" such ag lowering of% EF and */,aF Langendorff and perfused after administration of daunombicin in either wag observed. Puked Doppler examinationrevealed di~-tolic dysfunctionofLV - form to rats as six doses of 2.9 mg/kg every other day. Three parameters decre.~ed raio of enrly to lnte LV inflow velocity, deere.~ed of absolute were investigated : left ventricle developed pressure (LVDP), and deccelerntion of endy LV inflow. maximal and minimal derivatives of systolic pressure [LV(dP/dt)max Following exnmin~tionBperformed one month and 6 months after the and LV(dP/dt)min] which reflect the comractility and the relaxation eomple~tentntion of mthr~ydin~ md Catdiox~ne ~eatment showed a capacities of the heart, respectively. Treatment of rats with free daunorubicin induced a significant decrease comidernMeimprovement of the pm'nmetemanalyzed. C~diox,ane wag wall tolernted. of all three parameters, whereas daunoXome had no significant effects on these. Body weight and heart weight were significantly altered by Application of Cm'dioxane provides ,'m efficient protection of the free daunorubicin and daunoXome treatments, but the alterations caused cardiac toxicity &zring the treatment with anthrA,"yelinesin cancer dfildren and .~+ by daunoXome were less pronounced that following administration of might dimimshthe long-term eflect~ of the chemotherapy. free daunorubicin.

LVDP LV(dP/dt)max LV(dP/dt)min (mmHg) (mmHg/s) (mmHg/s)

129 PRgVENTION OF 5-FLUORURACIL (5-FU)-INDUCED control 89A + 9.7 2739 + 340 -1780 + 257 ACUTE GASTRODUODENAL INJURY *S. Sartori, I. Nielsen, L. Trevisani, D. daunorubicin 81.4 -I- 7.0* 2222 + 227** -1408 + 174" Tassinari, V. Abbasciano daunoXome 91.5 + 6.2 2754 + 230 -1700 + 196 II Divisione Medica, osp. S.Anna, Ferrara e Istituto di Medicina interna, italy. * p<0.05 ; ** p<0.01 versus control group

5-FU is known to induce mucosal damage to gastrointes= When peffused in isolated hearts of untreated rats, daunoXome had no significant effect, whereas free daunombicin induced marked alterations tinal tract. The aim of this randomized, placebo-cont= in contractility and relaxation. Heart accumulation was >10 times lower rolled study was to investigate the efficacy of Miso= when the drug was given as daunoXome than when administered as free prostol, Ranitidine and Omeprazole in preventing 5-FU- form. In addition, we have shown that daunoXome was able to keep the induced acute gastroduodenal lesions. antiproliferative effects of daunorubicin, since both drugs presented the same cytotoxicity in leukemia cells in culture. In conclusion, iii colon cancer patients with normal stomach and duode= daunoXome might be a safer form of administering daunorubicin, as it num or less than3 erosions, selected to be treated with displays similar in vitro cytotoxicity and reduced cardiotoxicity, 5-FU were randomly assigned to prophylactic treatment probably as a result of reduced accumulation in cardiac tissue with Misoprostol, Ranitidine, Omeprazole at standard dosages, or Placebo. 7 days after the end of the 2nd l ~4 AMELIORATIONOF CISPLATIN NEUROPATHY BY of 5-FU they underwent control gastroscopy. Endoscopic GLUTAMATE. findings were clustered into 5 classes, quantified on *Frances Boyle M B.B.S., Robyn Mot~k, Helen Wheeler the basis of an arbitrary score: O=normal; l=less than 3 M.B.B.S., Gillian Shenfield DM Depts. of Clin. Oncology and Clin. Pharmacology erosions; 2=3-15 erosions; 3=more than 15 erosions or Royal North Shore Hospital ulcer; 4=giant ulcer (diameter>2cm. After 5-FU, 12 (PC Sydney, N.S.W., Australia. 0.01), 12 (p~O.Ol), 9 (p~O.05) and 5patients developed mucosal injury scored as 2 or more in Placebo, Misopros= The effectiveness of Cisplafin therapy in malignant disease may be limited tol, Ranitidineand Omeprazole groups respectively. by the development of a sensory peripheral neuropathy. This may be Omeprazole was significantly more effective than Place= irreversible, leading to impairment of quality of life for cancer survivors. The amino acid glutamate is effective in preventing peripheral neuropathy bo in preventing the worsening of at least 2 points in due to Vincfistine (Boyle FM el at, Proc AACR, 1994). This study explores the score after 5-FU (VC0.05), whereas no significant its nsefullness as a neuroprotectant for Cisplatin in the same animal model, differences were observed between Misoprostol or Rani= which employs a battery of nettrobehavioural tests tidine and Placebo. Young adult Dark Agouti rats received Cisplatin 2mg/kg twice weekly IP. In conclusion, unlike cytoprotection exerted by Miso= Neuropathy was manifest as gait disturbance (toe-walking), an elevation of prostol, the strong and prolonged inhibition of gastric tail-flick threshold and impaired proprioception, measured by an acid production induced by Omeprazole seems to be able accelerating rota-rod test performed in the dark. Oral glutamate (4g/I in 371

drinkingwater) significantly delayed the onset of neuropathy, allowing immunoto• of this treatment. The higher doses to be tolerated. purpose of our study was to analyze the CispIatin Cisplatin + glutamate immunomodulatory effects of beta-carotene in patients with cromer in the ~a~' '7~e bowel. Max Tord Dose 34 +/- 2 43 +/- 8 Cancer' patients have received dai~y 30 mg (mg/kg) of beta-carotene for 2 weeks before the Gait Disturbance 90 % 16 % operation and were treated simultaneously (at week 8) by gamma-therapy in the total dose of 25 Tail flick Abnormal 50 % 0 % Grey. The irradiation therapy has caused (at week 9) 2-fold beta-carotenes reducing effect in Rota rod Abnormal 50 % 0 % the peripheral blood. F,eta- caz'otene (at week 9) supplementation proved to increase the l~mphocytes proliferation to mitogene This study demonstrates that peripheral neuropathy induced by Cisplatin can stimulus (PHA), the expression of surface be ameliorated by glutamate. Cisplatin and Vincristine have different fibre ]_ymphocy t e s markers ( CD25, CD45, CDw50, proclivities and intracellular targets, suggesting that the mechanism of HLA--]) as compared with patients treated by neuroprotection, currently under investigation, may generalise to other toxic gamma--therapy only. The augnnentation . of neuropathies. functional activity of natural killers was po~;Jtively correlated with hyperexpression of CD7 marker. Specific activity of T 132 OCT~EOTIDE IN THE PLACEMENT OF VENTING suppressor cells was significantly less in GASTROSTOMY IN PRESENCE OF MARKED BOWEL patients ti'eaLed by gamma - therapy plus DISTENSION. REPORT OF 2 CASES. beta-carotene thaw in patienLs treated by only. We consider the above ~S. Sartori,L, Trevisani, I. Nielsen, D. radiotherapy mention{:.~d beta carotene" s immunostimulatory Tassinari, V. Abbasciano. effect as the protection of lymphocytes II Divisione Medica e Istituto di Medieina from AL~nma--therapy-indueed damage_ Interna II, Ferrara, Italy.

Venting percutaneous endoscopic gastrostomy (VPEG) is 134 S,ADENOSYL4.-METHIONINE(SAME),POLIA- often used to achieve gastric decompression in small MINE SlNTHESYS AND RECOVERY FROM CHEMOTHERAPY - INDUCED ENTERITIS bowel obstructions due to abdominal carcinomatosis, P. La Ciura*, D. Perroni*, G.L.Grecchi*, A.Viglietti^ , but sometimes the interposition of distended bowel B. D'Angeli^ . *Medical Oncolog% ^ Division of loops makes impossible to obtain an appropriate apposi= Nuclear Medicine. S.Croce Hospital, Cuneo. Italy. tion between abdominal and gastric anterior wall. Mueositis, damage to the mucos~J lining o[ the gastrointestinal(Gl) tract and Somastatine and its analogue Oetreotide have been re= other mucosae, is, after myelosuppression, perhaps the most frequent dose- ported to have a powerful inhibitory action on gastro= limiting toxicity(tox) in oncolitic CT. ]'he growth of intestinal (int) mucosa comes from the balance between differentiation(diff.) and expression of intestinal secretions and to significantly reduce functional capacities. The basal cells in the cryptae express a typical int. bowel distension in mechanical bowel obstruction. function in their growth -the absorption- as a direct consequence of their diff. We administered Octreotide to 3 patients in whom it from the base up to the tip of villo. Among growing factors the polyamines (putrescine, spermine and spemidine) play a primary role in the diff. of this was not possible to place VPEG owing to marked bowel tissue and proliferation. The aim of the study: to evaluate the capacity of distension, hindering the endoscopic transillumination SAME(spermine and spermidine precursor) to overcome CT enterotox using of the abdominal wall, In two of them nasogastric drai= both clinical parameters and ~tChrome EDTA Test(~tCr Te), as indicators. 11 of 12 patients (pts) entered in the study were evaluable. Eligibility criteria: nage dropped from 1500-2000 ml/day to 250-S00 ml/day Age< 75 yrs, ECOG P.S. < 2, no alcohol intake, no acute or chronic int. after 2 days of subcutaneous Octreotide 0.i mg/8 hours. disease, no sepsi, no antidiarrhoic trt, grade(Gr) 2~ ~ WHO enteric lox. 24 VPEG was tried again: a good transillumination was hrs after symptom(sy) occurrence, all pts performed clinical and stools achieved and VPEG was placed without compl~cat]ons. examination , research for Clostridium Difficilis, blood test (expressive for absorption alteration) and ~lCr re, according to Ihe standard In our opinion, a two- or three-day long administrat= method(Bjarnason I.,1983) (n. v. range(r) 1,28 - 3,38 %). After ion of Octreotide should be attempted before abando= hospitalization SAME trt started, 500 mg x 3/day in 250 cr of NS water e.v. ning attempts at VPEG placement in patients with bowel infusion for 3 days, no antidiarrhoic trt was admitted except Ibr the hydration. 72 hls after trt start, control ~lCr te was performed. Symptomatic therapy obstruction and marked distension of" bowel loops. (toperamide, difenossilate, longostatine etc) was administered if diarrhea was still present after SAME trt. Pt Characteristics: 6 males, 5 females, median age 63 yrs (r. 50-72), 8 pts cole-rectal , 2 gastric, 1 head neck tumors; CT: 5Fu + Folinic Ac (9 pts), 133 IMMUNOCOf~~ BY BETA-CAROTENE 5Fu c.i. (1), DDP + 5Fu (1). WHO enteric tox. were: Gr 3~ 8 pts; Gr 2~ 3 IN CANCER PATIENTS pts. All pts were positive to the basal ~Cr te (r 3.51% - 22.1% -my. 1,28- *Regina Ramanauskaite, Ph.D. , 3,38%-). Results: 9/ l lpts had total symptom resolution within 72 hrs , Innesa Abronina, Ph_D. independently from the Gr. of tox . 1 pt had sympt resolution within 84 hrs Nontoxic immunomodulators lab (no antidiarrhoir trt). 1 pt had no response to trt (sympt resolution within 7 Cancer [{esearch C~ntre days with symptomatic therapy). 8 /11 pts had values normalization of S~Cr EDTA excretion within 72 hrs (r. 1,79- 2,98%). 2 pts showed values lightly Moscow, Russia higher than normal range, but with clinical sympt regression (3,55% and 3,99%). 1 pt had pathologic values (11,70%) and persistence of clinical One os the complications of oa,t i tumo:, symptomatology. Conclusions: Our data proved the activity of SAME in the gaaana-therapy is the decrease of ethiologic trt of CT-induced enteritis. The 51Cr Te may represents a good lymphocytes functional activity due to the method to define the damage of the enteric mucosa and its recover. 372

4 a~r~ ACUTE C~..DIAC TOXICIC EFFECTS (ACTE) OF HIGH DOSE graphically confirmed); a partial response (PR) as / ,t,#,tJ SEQUENTIAL CHEMOTHERAPY (HDSCT):RESULTS OF AN asymptomatic fluid recurrence not requiring further EPIDEMIOLOGICAL STUDY. *Lueio Patoia, M.D., Maurizio Coeehieri', M.D., Tiziana thoracocentesis within 30 days. Baglioni,M.D., Anna Rita Gobbini, M.D., Lina Marinaoci', M.D., Donatella Severini ", M.D., Albano Del Favero, M.D..lstituto di The fluid drained ranged 2,700-i0,600 ml (mean 6,300); Medlcina lnterna e Seienze Oncologiche and ~Unita' Operativa di catheters were removed after 10-25 days (mean 15.4). Cardiologia, Universita' di Perogia, 06100 PERUGIA, ITALY. CR was obtained in 6 patients, PR in 2; overall response HDSCT with autologus bone marrow / peripheral blood stem or rescue has been used for the treatment of lymphomas, multiple myeloma , high risk resectable breast carcinoma and rate was 80%. metastatic breast cancer (MBC) with promising results. To better define the toxicity profile of These preliminary results are very encouraging; in our HDSCT we investigated the ACTE era HDSCT regimen used in our institution in a phase I-II trial for the treatment of MBC. In fact, the ACTE of conventional doses of the drugs opinion, the careful monitoring by ultrasounds may have employed in the HDSCT regimen are known, but the cardiotoxieity of high doses and of the played an important role in obtaining them, allowing sequence is not sufficiently investigated. METHODS:HDSCT:Cyelophosphamide (CTX) 7gr/sqndiv day (d) I, Methotrexate (MTX) to instil Bleomycinwhen the pleural fluid was drained 8gr/sqm/iv and Vincristinr (VCR) 1,4mg/sqm/iv d 18 ,Doxorubicin (DOX) 125mg/sqm/iv or completely and the pleural layers were in contact as Epirubiein (EpiDOX) 120mg/sqm/iv - 175mg/sqm (2 cases) d 25 , CDDP 60 mg/sqm/iv d 35 and d 42 , Melphalan (L-PAM) 200mg/sqm/iv d 52 or L-PAM and Thiotepa 600mg/sqm/iv much as possible. (I case). CARDIOTOXICITY EVALUATION: clinical examination , ECG , ~24hours-ECG- HOLTER (HOLTER) , Echoeardiogram bi-mode (ECHO) were performed before and after every cycle of chemotherapy. RESULTS: 18 female patiems (pts) ,[ I pretreated , with metastatic ( 13 ) or adjuvant ( 5 ) breast cancer, mean age 47 (range 31-59), were evaluated. RISKS OF THE TOTALLY IMPLANTED Clinical examination: no eases of congestive hearth failure or symptomatic angina or ECG 137 signifieative alterations occurred. ECHO bi-mode: 18 pts evaluated ; all the pts had a normal CENTRAL VENOUS CATHETER: ECHO with a left ventricular ejection fraction (LVEF) > 50% at the basal evaluation; 1/18 RELATIONSHIP TO TUMOR TYPE had a fall in LVEF (44%) after MTX-VCR administration, which reverted to > 50% 7 d *Daniele Marceau, M.D., Kathleen later. 6/18 03%) eases of minimal perieardial effusion (2/18 after CTX, 3/18 after MTX- VCR and 1/18 after L-PAM) and 6/18 03%) cases of hyperechogenie cardiac masses of Duchesneau, M.D. and Peter Bogaty, M.D. unknown origin (4 after CTX and 2 after DOX ).In all the cases a possible relationship Laval University, Quebec between chemotherapy and cardiac masses seems to occur. In fact: 1. all the pts had a normal Quebec Canada. ECHO at basal evaluation; 2. it is very improbable that they could be of metastatic origin , given the disease status of the pta and the occurrence during HDSCT; 3. in 4/6 cases the lesions were transient and the nuclear magnetic resonance (NMR) was not indicative of a The risks of the totally implanted central venous catheter metastatic lesion in the only case studied with NMR. 4/18 (22%) cases of regional left (TICVC) and the relationship of risk to tumor type are poorly ventrieular hypokinesia (1 after CTX ,2 after MTX- VCR ,1 after CDDP);4. The clinical defined. We evaluated our experience in 123 consecutive conditions and blood cultures were not indicative of an infective origin. ROLTER:asymptomatie ST-T depression were documented in 1/11 (9%) case during CTX , TICVC insertions (112 pts) over 4 yrs. There were 70 women 1/8 (12,5%) case during DOX and 1/12 (8,3%) case during L-PAM ; atrioventricular block and 42 men, mean age 40 yrs (range 4 to 74 yrs); mean 2:1 Mobitz II in 1/9 (11%) ease during M'TX-VCR ; ectopie atrial taehicardia in 211t (18%) duration of implantation was 46 wks (range 1 to 156 wks). cases during CTX; 1/23 pts (4,3%) treated with HDSCT developed a eardiogenic shock and died 6 days after L-PAM. All the cardiac evaluations performed before and during HDSCT Follow-up was to TICVC excision, death or end of the were normal. The administration of every drug was associated with the following rate of observation period, whichever came first. Underlying disease abnormalities at ECHO/HOLTER evaluation: CTX 39 % at ECHO and 27% at HOLTER, was solid tumor in 56 pts (50%), hematosarcoma in 53 VCR-MTX 33 % /25 %, DOX I1% /62 %, CDDP5 % / 17,6 %, L-PAM 5 % / 33%. CONCLUSIONS: the rate of fatal ACrE associated with HDSCT seems to be low, whereas (47.3%) and miscellaneous in 3 (2.6%). There were 4 a number of asymptomatic and clinically not relevant abnormalities were found with a immediate complications (pneumothorax) and 41 late systematic, not-routinary, strumental evaluation. Generally, the non fatal ACTE are complications (24 infections, 8 central venous thromboses, 8 reversible, not cumulative with the sequential administration of drugs, and not predictive of more severe clinical events. Further studies on larger number of pts, ECHO-Doppler dysfunctional catheters and one right atrial migration). Of the evaluation of left ventricular diastolic function and the assessment of chronic toxicity seem to infections, 15 (63%) had positive blood cultures and death be warranted and are ongoing to better precise the ACTE of HDSCT. occurred in 7 (29%). Incidence of infection was similar in solid tumors and in hematosarcomas. However, 5 of the 10 leukemia pts had TlCVC infection and 4 of the 7 TICVC 136 UL~,ASO~NDMONITORING OF MALIGNANT infectious deaths occurred in these pts. Of the 8 thromboses, PLEURAL EFFUSIONS AFTER SMALL-BORE 5 occurred in the 24 pts with Hodgkins disease, none of whom had tumor central venous compression. No death was CATHETER PLACEMENT. PRELIMINARY RESULTS. attributed to thrombosis but the latter caused one pulmonary ~S. Sartori, L. Trevisani, I. Nielsen, D. embolism. Thus, complications are frequent in TICVC and pts Tassinari, A. Maestri, V. Abbaseiano with hematosarcomas appear at particular risk. TICVC II Divisione Mediea e Istituto di Medieina insertion may be inadvisable in leukemia pts. Interna II, Ferrara, Italy.

Effusion recurrence is a major problem in the palliative care of patients with disseminated cancer. 138 EXPERIENCE WITH IMPLANTED VENOUS Intrapleural 8-French catheters were placed under sono= ACCESS PORTS IN 79 CANCER PATIENTS. graphic guidance in i0 patients with recurrent pleural *T.Bauernhofer1 ,A.K.Kasparekl,H.Strger 1 ,M.Schmidl effusions requiring at least 2 thoraeocenteses/month. R.Moser1,F.Ploner 1 J.Kuss 1,D,Dakar2,,H.Samonigg 1 Chest ultrasounds were carried-out daily and effusions 1 Department of Oncology, 2Department of Surgery were drained until ultrasound monitoring showed com= KarI-Franzens-Universit&t Graz,Austda plete absence of intrapleural fluid. Afterwards, Bleo= mycin 20-40 mg through intrapleural catheter, which was Safe and pain-less vascular access is an achievable goal kept closed for 12 hours and then opened again for 2 for every patient receiving long-term intravenous days: if output was less than 50 mi/24 hours, catheter systemic chemotherapy or supportive care. The aim of was removed. A complete response (CR) was defined as no this retrospective study was to evaluate the complication further reaccumulation of fluid within 30 days (sono= rate of implanted venous-access ports in our institution. 373

Within the last 8 years 72 single-lumen and 7 double- 140 AMBULATORY LONG-TERM I.V. lumen venous-access ports have been implanted in 79 INFUSIONS OF CYTOSTATICS THROUGH cancer patients (51 females and 28 males). The median A NEW DISPOSABLE PUMP SYSTEM age of the patients was 41 years (range 16 - 75) and the Leif Stenke, Marita Lindberg*, Tiina Rintala, treatment intention was palliative in 43, curative in 33, Mikael SvenssonO and Anne Maj Esberg adjuvant, neoadjuvant and supportive in 1 patient, Div of Haematology, Karolinska Institute at Danderyd respectively. 44 patients received standard-dose hospital and the Hospital Pharmacy0, Danderyd, Sweden. chemotherapy in an outpatient setting, 34 patients were Long-term i.v. infusions of cytostatic drugs are usually adminis- treated with more intensive systemic chemotherapy tered through electronically controlled pump systems, a proce- regimens in an inpatient setting and home parenterat dure which often confines the patients to prolonged periods of nutrition was administered to 1 patient. Either a 19- or 22- hospital care and involves high costs. We have tested drug deli- gauge Huber or Gripper-needle was inserted in the very through a new, disposable infusion system, the subcutaneous port-chamber and was flushed with Homepump| (Nycomed), in which a multi-layer elastomeric heparinized saline (100 units heparin/ml saline) before membrane generates positive pressure without the requirement of programming or batteries. Six patients were given a total of 10 the first and after each infusion or at least every 3 courses of long-term infusions of cytostatics. Four patients had months. 3 port-related cases of sepsis, 1 infection of the multiple myeloma, two chronic myetoid leukaemia. The median port pocket, 1 thrombosis of vena subclavia, 1 skin age of the patients was 66 yrs (range 53-79 yrs). Eight of the erosion, 2 postoperative hematomas, 2 drug chemotherapy infusions included vincristine and doxorubicin extravasations, 3 catheter malpositions and 3 catheter (given together with steroids in the "VAD" regimen), two thromboses were observed. The first 4 types of courses included ara-C. After filling of the pump, the drugs were complication made an explantation of the port in 5% given through i.v. lines (9/10 central) as continuous infusions (6/79) of patients necessary . All other complications during 72-120 hours with flow rates of 1-2 ml per hour. could be managed conservatively. In conclusion All infusions could be completed as planned without any implanted subcutaneous venous access ports are well unforeseen interruptions. None of the patients experienced any accepted from both patients and medical personnel with major inconveniences from the pump. During 7 of the 10 an overall rate of complication of 11%(14/79). courses, the patients spent the majority of the infusion interval outside the hospital. The delivery time accuracy was acceptable in most cases, but in one myeloma patient the vincristine/doxorubin infusion was completed already after 72 hours instead of the 139 IMPLANTABLE ACCESS DEVICES planned 96 hours. This 25% inaccuracy was probably due to CATETKER OR PORT - PLUS ELASTOMERIC increased temperature (the pump was kept close to the skin of the PUMPS FOR NEOPLASTIC ELDERLY patient who was in bed with continuous fever). OUTPATIENTS TREATMENT We conclude that the disposable Homepump| infusion system *A. Abbadessa,, R. Muscher-,i, SGiordano appears to provide a reliable and cost-effective i.v. delivery of *Diparfimento Internistica Clinica Sperimentale cytostatics with the potential of ambulatory drug therapy. 'F.Magrassi, Seconda UniversitY; Uni~ Operativa However, we recommend central i.v, lines and strict routines to Ematologia Oncologia - Napoli. minimise complications and to choose regimens where major deviations in the delivery time can be accepted. Introduction: In the elderly patients there is a increase of the incidence of the cancer diseases and there is necessary to cause the new systems for to administer the treatment.. The employment of elastomeric pumps ASSESSMENT OF THE ECONOMIC VALUE OF for continous intravenous infusion togheter with permanent central 141 GEMCITABINE (GEMZAR| IN NON-SMALL CELL venous accesses could provide an adequate treatment on outpatient LUNG CANCER basis and avoids prolonged hospitalization and bed-stay for elderly *Catherine Copley-Merriman~, Christophe Martin, Peter Koch, patients with advanced-stage cancer. Josc A Sacristan, William K Evans, Peter Drings, Nick Materials and Methods: Eighteen elderly cancer patients in advanced Bosanquet. stage ( median age 74, range: 70-81; colorectal: 6; gastric: 1; breast LLilly Research Laboratories, Lilly Corporate Centre, cancer: 1; refractor3, NHL: 2; lung 2; CML blast crisis: 2; refractory Indianapolis, Indiana, USA. AML: 4) were treated by means of elastomeric pumps (Multiday Infusor Baxter) together with central venous devices (Groshong 2; Although cost considerations have not traditionally been important in cancer Hickman 9; Port-a-Cath: 7) for a total amount of 65 cycles of treatment decision making, there is increasing concern worldwide about the antiblastic therapy. economic impact of therapeutic alternatives in oncology. In particular, there is Results: All the patient found elastomeric pumps to be practical and greater pressure for pharmaceutical companies introducing new products to quite tolerable owing to their lightness and silence. Six patients who assess the economic value of products prior to launch. We have investigated and had previously refused chemotherapy, became compliant to an compared the clinical outcomes and corresponding cost savings of a new outpatient treatment. No sepsis, nor obstructive complications have chemotherapy agent, gemcitabine (Gemzar| with other chemotherapy options been observed. Median time of hospitalization was short (17 days; in four different health care settings: the United States, Germany, Spain and Canada. Most of the work with Gemzar * has been done in non-small cell lung range 0-70 days), if compared with a median time of 4 months in cancer (NSCLC). Most NSCLC patients present with advanced disease which folIow-up. Furthermore, the availability of a permanent central line is unsuitable for surgery, and in many cases, unsuitable for potentially curative allowed a supportive treatment, transfusional and antimicrobial, in a chemotherapy. Chemotherapy for the majority of patients is therefore home care setting and proved very useful for palliative care of patients administered with palliative intent. For this reason, the comparative agents who chose to die at home. chosen for the economic models were palliative treatments (cisplatin/etoposide Conclusion: The implantable acces devices catether or port plus and ifosfamide/etoposide), or best supportive care. elastomeric pumps are the good system for to admnister the treatment As is customary with oncolytics, Gemzar| was investigated first as a in the elderly patients that don't prefer a prolonged hospitalization. single agent in non-comparative trials. Since data were not available from a 374

comparator trial, we estimated comparator data from the literature sources and agent is used, often on a long infusion schedule with expert opinion (German and Spanish cost models), retrospective chart reviews a pump delivery system. The use of a suitable radio- (US cost model), and a combination of expert opinion, database analysis, and nuclide for infusion may offer the advantage of a surgeon and oncologist surveys (Canadian cost model). While the four economic single dose, technically convenient method of HAIT. models of Gemzar | monotherapy used different comparators and methodologies Towards this end, Y-90, a short half-life and short and targeted different health care settings, all four models demonstrated cost range beta omitter is being studied. Yttrium-89 oxide savings or cost-effectiveness (Canadian model) for Gemzar| is incorporated into the matrix of glass microspheres The three economic models comparing Gemzar | monotherapy to other and converted to radioactive Y-90 by neutron bombard- chemotherapy regimens identified several clinical features of Gemzar| therapy ment (Theragenics Corporation). In all pts a baseline that may translate into cost savings: convenient 30-minute infusion not requiring hepatic arteriogram is done and Tc99m macroaggregated hospitalization or aggressive hydration; limited incidence and severity of nausea albumin liver perfusion and l

DAY OF ASSESSMENT (DA) AND QUESTION of energy were significant problems. Significant variability was 145 TIME FRAME (TF) AFFECT REPORTED QUALITY recorded by patients in their overall ratings of their quality of OF LIFE (QOL) AFTER MODERATELY life. However, even in this small pilot study it is apparent that the EMETOGENIC CHEMOTHERAPY (MEC)*. J Pater ~, quality of life in multiple myeloma patients is fairly poor and the MJ Palmer~ B Zee 1, D Osoba~, WS Lofters j , C Chin2, assumed improvements following treatment are at best marginal. E Dempsey2, ~National Cancer Institute of Canada Sequential studies which follow the patient through from diagnosis Clinical Trials Group, -~Marion Merrell Dow Canada until death are needed to establish a valid framework, whereby the Research, Queen's University, Kingston, Ontario, value of available treatment options may be objectively assessed by Canada K7L 3N6 -both medical professionals, and indeed patients, in quality of life Nausea and vomiting (NV) after MEC is usually most severe in the first few tems. Clearly as individuals evaluate and choose between treatments, days after treatment and resolves by the end of one week. In a previous it is crucial that quality of life issues are borne in mind, and this study (J Clin Oncol 1994; 12(5): 1050-1057) we found modest correlation n~!ected are~ of st,.~y in myelama is fully addressed. between control of NV and QOL measured at day 8. We postulated that, despite the 7 day "IT of the questionnaire, patient (pt) assessments reflected A LONGITUDINAL STUDY OF QUALITY OF the most recent days' experience. We therefore developed this study to 147 LIFE (QOL) ASSESSMENT IN PATIENTS explore whether administering a QOL questionnaire at different days after PARTICIPATING IN PHASE III CLINICAL MEC and/or with a different TF would affect the results reported. 696 pts TRIALS FOR SMALL CELL LUNG CANCER participating in a clinical trial of anti-emetic regimens for MEC were *Kenji Eguchi, M.D, Mihoko Kanazawa, randomized by centre in a 2X2 factorial design to complete the EORTC R.N., Kinuko Tajima, M.S., Tomohide Tamura, QLQ C30+3 prior to chemotherapy and on day 4 or day 8 after initiation of M.D., Nagahiro Saijo, MD., from the Lung chemotherapy, using a 3 or 7 day TF. For each pt, results were expressed Cancer Program of the Japan Clinical Oncology Group in terms of change in QOL scores from baseline (CS) for each component of the QLQ C30+3. A general linear model was used to analyze the effect of Purpose To examine the practicality of longitudinal DA and TF, controlling for the effect of antiemetic regimens. Initial assessment of quality of life (QOL) in patients analyses indicated that there was an interaction between the effects of DA and participating in multicenter randomized clinical trials. TF on social function (p=0.068), global QOL (p=0.001), and NV Patients and Methods From May 1991 to January 1995, (p=0.004), Results are therefore presented separately by DA and TF, the Japan Clinical Oncology Group (JCOG) conducted two Patients completing the QLQ C30+3 at day 4 had significantly worse social randomized phase III clinical trails for patients with function than those at day 8 with the 3 day TF (CS: -11.4 versus -1.l; small cell lung cancer. Patients with extensive disease p=0.0027) but not with the 7 day TF (CS: -7.8 vs. -6.4; p-0.678). received either a weekly CODE regimen (9 weeks) or an Patients completing the QLQ (330+3 with 7 day TF rather than 3 day TF alternative EP+CAV regimen (18 weeks). Patients with had significantly worse global QOL (CS: -10.3 vs. -1.2; p=0.00l) and limited disease received either concurrent symptoms ofNV (CS: 21.1 vs. 13.4; p=0,007) at day 8, but not at day 4 chemoradiotherapy (12 weeks) or chemotherapy (CS for global QOL: -5.6 vs. -8.4, p=0.282; CS for NV: 14.5 vs. [8.4; followed by radiotherapy (16 weeks). Successive QOL was p=0.163). We conclude that both DA and TF affect patient reports of QOL assessed weekly during the treatment period with a 42- after MEC. The first is not surprising, given the time course of NV after item questionnaire translated and modified from EORTC- MEC. However, the fact that patients distinguish between 3 day and 7 day QL. Results Successive data from 202 of 228 (89%) TFs was unexpected, and, we think, noteworthy. patients with extensive disease and from 213 of 231 (92%) patients with limited disease were collected from the 17 participating institutions. In patients with limited 146 QuALiTy 0r LrE sEss,E r I, disease, there were significant improvements in ~LTIPhE MYESOMA. physical, psychological, and global QOL scores and Alastair Smith FRCP *Shirley Crofts EC significant decreases in the domain scores for patients' Department of Haematology relationship to family and friends (ANOVA, p=0.0003, Royal South Hants Hospital Southampton, Hampshire, United Kingdom. 0.0299, 0.0099, and 0.0150, respectively). In patients with extensive disease, there was significant improvement in Psychosocial issues cover a large area, of which quality of life is only the physical domain (p=0.0027). The QOL results of but a small part. Measurement of health related quality of life is each arm will not be compared until the end of the included in many clinical trials, but has remained largely ignored in follow-up period. Conclusion~ Longitudinal assessment studies of myeloma. Treatments are evaluated using pathological and of QOL in large-scale multicenter randomized trials is radiographical measurements. If treatment has been successful using practical. We will continue to assess QOL until 3 years these criteria, it is almost universally assigned that an attendant after treatment or until patients are unwilling or improvement of quality of life is tbe given outcome. Our impression unable to respond to questionnaires. from clinical experience suggested that this ass~ption was not valid. Quality of life becomes an even greater issue in the absence of 1 48 CLINICAL STUDY ON THE EFFECT OF curative treatment or early diagnosis of myeloma and must be part of ~THYPREDNISOLONE ON THE the criteria used to help assess the benefits and limitations of QUALITY OF LIFE IN PATIENTS IN PRE pre~ntly available approaches. We set out to measure quality of life TERMINAL STAGE OF MALIGNANT directly, using three validated questionnaires. In this preliminary DISEASE; COMPARISON OF study patients with multiple myeloma at different points in the course PARENTERAL AND ORAL ROUTE OF ADMINISTRATION of their disease and treatment were asked to complete the *Sini~a Radulovid, M.D., Dejan Konstatinovi~, questionnaires. There were 21 participants, aged 49 to 85 years( mean M.D., Labuda Vulet/~, M.D. = 65 years). The type and stage of treatment varied;- 6 were in Institute for Ontology and Radiology of plateau and off treatment, 2 were post transplant, 4 were receiving Serbia, Belgrade, Serbia-Yugoslavia C-VAI(P, 3 were on melphalan § prednisolone, and 6 were on dexamethasone. The results showed pain to be the main problem in all In an open, randomised, comparative study the efficacy and safety of groups regardless of treatment. Reduced mobility, tiredness and a lack methylprednosolone (MP) on quality of life of the patients with 376 preterminal stage of malignant disease was studied; parenteral (iv. or 150 IMMUNOTHERAPIES FOR MALIGNANT ira.) and oral administration of MP was compared. Total of 60 pts DISEASES - ILLUSIONS AND REALITY with advanced malignant solid tumours and symptoms of nausea/vomiting, pain, cachexia, lack of appetite or other symptoms *Simon P. Hauser, M.D., Markus C. were randomised to receive 125 rag/day iv. MP or 160 rag/day po. MP. Allewelt, M.D. Patient were treated at their homes, verbal informed consent was Swiss Cancer League, Monbijoustr. 61 obtained and treatment lasted for four weeks or until death. After CH-3001 Bern, Switzerland four weeks the results were evaluated and the treatment prolonged according to the discretion of the investigator. The efficacy was assessed by LASA scale and FLIC, Physician Global Evaluation Scale In recent years, cancer patients are increasingly and safety by side effects, laboratory finding and four-grade scale. MP confronted with reports on various unspecific and specific increased appetite, well being, quality of sleep and ability to carry active Immunotherapies as treatment or adjuvans for some house work. MP decreased feeling of weakness, powerless, depression, the usage of supportive therapy especially analgesics. The different tumors. Patients and doctors are asking the effect was obvious approximately after 2 weeks of the treatment and Study Group on Unproven Methods in Oncology of the efficacy and safety of iv. MP was superior comparing to oral MP. IV Swiss Cancer League for information and the efficacy of MP significantly increased patients performance status. Safety of MP these therapies. Here we present the theory and was judged as GOOD. Half of the patients experienced abdominal pain during the treatment with oral MP. Infections, soor and investigations 5 different immunotherapies which are gastrointestinal bleeding were more frequent in group receiving oral commercially offered to patients with various tumors: 1. MP. Active Patient-Specific Immunotherapy (APSI) of Tallberg produced by Vitorgan GmbH, Ostfildern (cost per cycle DM 1029.-); 2, Autologous Target Cytokine (ATC) Therapy of Klehr, Munich (ca. DM 3000.-); 3. Immuno- Augmentative Therapy (IAT) of Burton (initial week ca. DM 2100.-, thereafter DM 100.- per week); 4. Theraccine of K0bler, Munich (cost ?); 5. Autohomologous 149 ETHICS CONSULTATIONS IN ONCOLOGY: THE Immunotherapy with activated Macrophages (AHIT-a-M) NEGATIVE IMPACT OF NEGATIVE LABELS of Kief, Ludwigshafen (cost ?). Only the original APSI of *Kristi Skeel Williams, M.D., Joy D. Skeel, M.Div., G. Bennett Humphry, M.D., Roland T. Skeel, M.D. Tallberg who combined it with a polypragmatic Departments of Psychiatry, Medicine & Pediatrics "biotherapy" was clinically tested, however, with Medical College of Ohio questionable success. The other immunotherapies have Toledo, Ohio, USA not been tested in clinical studies. Manufacturing procedures are at least in part secret and the final PURPOSE: To report our experience on the application of negative labels to patients with cancer or their families or both and to relate product is poorly defined or unknown. Despite promising how this negative labeling may affect supportive care. The claims by the producers, immunotherapies in oncology application of labels to the parents of children with cancer or adult are still of experimental nature and clinical data, if any patients with cancer or their family members by one or more are available, are unfavorable for routine applications. members of an oncology team was found to be an ethical problem through experience gained while one or more of us were involved in the Ethics Consultation Service. DESCRIPTION: Consultations in Ethics were requested by the attending physician, nurse, or social worker. The general reason USE OF TRADITIONAL CHINESE for requesting an ethics consultation stems from conflicts among 151 MEDICINE AMONG ASIAN CANCER family/patient or members of the oncology team. Retrospective PATIENTS review of issues involved in Ethics Consults revealed that negative Koo WH, *Toh H C, Ang P T labeling surfaced as an unidentified and compounding problem. Only rarely was negative labeling identified as the primary reason Dept of Medical Oncology for the consultation. The reasons given for the requested Singapore General Hospital, Singapore consultation were in general: 1. Termination of life support; 2. Failure of the faculty to disclose diagnosis, prognosis or the end- Alternative medicine is increasingly popular in both Asian stage status of the patient; 3. The insistence of one member of the and Western societies. More than 50% of cancer patients oncology team to recommend experimental chemotherapy or bone (pt) treated in Singapore General Hospital tried traditional marrow transplantation in the face of an extremely poor prognosis. Chinese medicine during the course of their illness. A These issues are difficult enough in a spirit of team cooperation, but survey conducted among 406 cancer pt showed that many become compounded when disrespect is shown to the patient or of these pt were young (68% of pt <60 year), well-educated family by applying labels such as "dumb", "demanding", "stupid", (70% of pt with at least college education), and English- "not worth my time" or even "psychotic". educated (52% of English-speaking pt). 201 pt (49.5%) CONCLUSION: Negative labels should be avoided. The with a median follow-up of 9 months were taking traditional inadvertent use of a negative [abel by a team member should be Chinese medicine at the time of interview. With longer identified by other team members when it is first applied to a follow-up (median 21 months), another group (57 pt) had patient. A team commitment not to use negative labels as a general principle of supportive care can be helpful, but requires an open stopped. Most commonly used Chinese medicine was exploration of a team's performance and capacity for self-criticism. commercial over-the-counter preparations like capsules, Ironically, while negative labeling is discussed in the mental health powder and mixtures (41%). Tonics like birds' nest, literature, reviews on psychosocial oncology seldom mention this ginseng were also popular (39%). The majority of these important area. products were obtained from local Chinese medicine shop 377

(60%). 33% of pt believed that Chinese medicine home. They usually come to their community augmented the immune system and 26% thought it would hospital also in the terminal phase, where reduce toxicity of conventional treatment. 64% of pts on they had been treated before. Due to a sub- Chinese medicine felt subjectively better. 9% actually saw speciality in hematology-oncology, a signi- objective improvement in laboratory tests and attributed ficant number of cancer patients is treated that to Chinese medicine. 54% of pt said they would stop through their disease at our hospital inclu- on advice by their oncologists, but only 37% consulted ding the terminal phase. This poses a heavy them. The majority of pt (89%) did not think Chinese burden of responsibilty and psychological stress to nursing staff and docor.s. It was medicine was harmful. The use of alternative medicine is postulated that essential aspects of pallia- a significant problem. More analyses and data on tive care could be provided as integrated traditional Chinese medicine are required for an informed part of the regular hospital work, if i) the decision on their objective and not just anecdotal efficacy staff is moderately expanded, 2) continuing and benefits. education in palliative care is established and 3) a type of supervision is provided. This was granted by the Deutsche Krebshilfe 152 DEVELOPMENT OF A PALLIATIVE CARE PRO - for a three year period starting Jan. I, GRAM (PCP) IN A TERTIARY CARE CENTER 1995 *) A documentation system was developed IN THE UNITED STATES to evaluate the medical and nursing measures Cleveland Clinic Foundation, Cleveland of symptom control, and the acceptance of the USA patient and the family. From Jan. to May, 34 Walsh TD, Goldstein P patients were cared for in this projekt. 18 died at the hospital. Improved symptom con- Mortality from cancer is increasing. Palliative Care trol and intensive involvement of the family is an esse~Itial part of the spectrum of cancer care. were the maior documented benefits of the We report on the development and current status of a program. For terminal cancer patients in PCP-the first program of its kind is the USA. The rural areas the ideas of the hospice move- program provides specialist continuing care for the ment (:an at least patially be integrated complications of advanced cancer e.g. pain, using a into the regular work of a general hospital, multidiseipllnary team, conducts research and pro- if certain requirements are fulfilled. vides education about these problems. The PCP started *) Grant # 70575 der Deutschen Krebshilfe. in 1987 with an inpatient/outpatient consultation service; outpatient clinics (1988), physician fellow- ship training (1989), inpatient service (1989), hos- pice home care service (1990) and dedicated 23-bed 154 ATTITUDE TOWARDS inpatient unit (1994) followed. PALLIATIVE OR EXPERIMENTAL We have examined the clinical and financial re- TREATMENT - A COMPARATIVE cords for the PCP for 1994 to provide aN overview STUDY OF PATIENTS, of the impact of a PCP in modern cancer care. The RELATIVES AND NURSES PCP accounted for 22% of new clinical actiyity for WH Koo, A Lee, *Toh H C, PT Ang. the Department of Medical Oncology and generated a Department of Medical Oncology major portion of home care activity. New consults Singapore General Hospital, Singapore 0316 for the PCP increased 15% in 1994. 570 new patients were referred to the program of whom 274 were cared Cancer patients are more likely to accept treatment for by the hospice home care service. Clinical act- ivity has increased ~ 100% since 1988. The program with minimal chance of benefit than those without now has three full-time attending physicians, three cancer. This is reflected in a survey conducted clinical fellows, 60 staff and i00 volunteers. Fin- among patients and their relatives where 55% ancial analysis revealed the program has the same (n=128) of patients were willing to undergo either contribution margin 42% and a more favorable 14% net palliative treatment (PT) or experimental treatment income/net revenue compared to other areas of medical (ET) whereas only 37% and 27% of immediate oncology. Overall the PCP generated 15% of the new relatives (n=97) were willing for their relatives to revenue for the entire department. undergo PT and ET respectively. Immediate We have demonstrated over a seven year period the relatives were directly involved in supporting a clinical value and financial viability of a PCP. A family member afflicted with cancer. A third group, PCP has a major role in modern cancer Care. Provis- that of oncology nurses (n=101), were also ion of such services should be mandatory. surveyed. Only 7% and 24% of nurses were willing to undergo PT or E-r respectively, and only 12% INTERGATED PALLIATIVE CARE and 22% were willing for an immediate relative to 153 IN A GENERAL RURAL COMMUNITY undergo PT or ET respectively in a hypothetical HOSPITAL scenario. This likely reflected the nurses' *Wolfgang 8ehreml, M.D., Georg background understanding of chemotherapy, its Kafka, M.D., Jens Staub, M.D. efficacy and potential toxicity. Interestingly, nurses Dept. Internal Med., Kreiskran- kenhaus, 89312 G~nzburg, Germany were biased towards ET while relatives preferred PT when it came to deciding for their relatives. For terminal cancer patients in rural areas, In Asian societies, many patients are not aware of hospice care is rarely accessible close at their diagnoses. Decisions to initiate treatment are 378

often made by family members or health care short, medium and long durations) given in three common malignancies. Results are below: professionals. The above study reflects the concern TOTAL COST IN: that a significant number of patients may not TREATMENT CLINIC CARE HOME CARE receive potentially beneficial cancer chemotherapy 5-FU/LV $151 (5 days) $799 (5 days) if this trend continues. CTX+ADRIA $249 (i day) $797 (I day) VPI6+DDP $1096 (3 days) $2196 (3 days) TRANSFUSION $359 (2 u RBC's) $435 (2 u RBC's) AMPHOTERICIN $181 (I day) $277 (i day) 1~1~ NEW POSSIBILITIES OF SUPPORTIVE CANCER In each treatment type, clinic was less expensive 1 ,Ill'l/# than home care, in a busy out-patient setting in CARE IN POLAND which economies of scale could be realized (range: *Malgorzata Symonides, M.D., Jerzy Jarosz, M.D., 21% to 429%). To control for the lower drug Ph.D., Maciej Hilgier, M.D., Ph.D. acquisition costs found in the clinic setting, costs Dept. of Anaesthesia, Cancer Pain and Palliative were also examined independent of pharmaceuticals; qSre~m~ent Center, the clinic setting remained less expensive (range: 49% to 393%). We conclude that while both clinic and Maria Sklodowska-Curie Memorial Cancer Center and home care are alternatives to inpatient treatment, Institute of theology, Warszawa, Poland, an efficient out-patient clinic setting is associated with greater cost savings than home care. The frequency of applying intensive care and palliative therapy in theology has increased over the past years although the number of establishments providing such care is rather limited. Recently a major HOME TREATMENT OF CANCER national anticancer center - The Maria Sklodowska-Curie Memorial 157 PATIENTS IN NEW BELGRADE Cancer Center - Institute of Oncology has been opened in Warsaw, *Dejan Konstantinovi6, M.D. Poland. The original canter has been established by Mine Curie, but being Health Center New Belgrade, rather limited in size it consisted of only four wards, approx. 140 beds Goce Del~eva 30 (incl. 6 beds in a surgical ICU). The old center is now being converted 11070 New Belgrade, F. R. Yugoslavia into an educational facility aimed at pre-graduative oncological training, whereas the new center combines eleven hospital wards with outpatient clinics and research laboratories. (It also has two branches in two other l'olish cities - Gliwice and Cracow.) The hospital wards (altogether 536 During the last 15 years special teams develop their activities in beds) are organ orientated, which differs from the traditional division into all biger towns of Serbia, in organizing the services for home therapeutically organised wards, (i.e. surgery, chemotherapy and radiation treatment and medical care. They are organized as particular therapy), while the Department of Anaesthesia is one of the common links units in the frame of primary health care. The scope of their of the whole hospital. It combines two units - an ICU ( 12 beds) mainly works is multidisciplinary and has features of both primary concerned with the treatment of surgical patients but also capable of and hospital health care. The most responsible member of the providing general IC, and a Cancer Pain and Palliative Treatment Center team is general practitioner (specialist of G.P.), having specific (8 beds) which is designed to provide active palliative treatment and and continius education. The teams practice all therapeutic which also runs a Pain Clinic for outpatients and which cooperates directly procedures at home, including infusiones, transfusiones, with the Warsaw oncological hospice. oxigenotherapy, supportive therapy etc. They also used We wante d to present this outline of anticancer treatment in Warsaw laboratory examinations, ECG, and other anxiliary diagnostic because we believe that its modern organisation and the wide range of methods. Home treatment is assigned to all adults who suffer medical services which it offers (including pain treatment) may well be from an acute disorders, when hospitalisation is not necessery. worth recommending. Among the patients treated by intensive home treatment, malignant diseases are dominant (above 3100 pts, or 37% of all treated pts.). This method of care (intensive home 156 ALTERNATIVES TO INPATIENT CARE: A COST COMPARISON OF HOME VERSUS OUT-PATIENT treatment) has a particular importance for cancer patients in CLINIC CARE FOR CHEMOTHERAPY AND advanced and terminal phase, when everyday treatment at SUPPORTIVE CARE MEASURES. home represents the adequate solving of their biological and *MM Trapani, RJ Gralla, PA Grusenmeyer, psychosomatic problems, higly improving their life conditions, and MM Bateman. Ochsner Cancer Institute, quality of life, and meets all their needs. The complications of New Orleans, Louisiana USA. malignant diseases, as well as those arising after specific Advances in supportive care have encouraged new therapy, are successfully dealt with cooperation and approaches in the delivery of cancer treatment. consultation with the Institute for Oncology and Radiology of Effective control of emesis, new chemotherapy administration methods, and awareness of approaches Serbia, in Belgrade. to febrile neutropenia have contributed to these changes. Administration of chemotherapy outside of a hospital setting can provide greater patient and family satisfaction and the potential for major cost savings as previously shown with 440 patients in a 158 QUALITY OF LIFE SCORE PREDICTS BOTH randomized study. In that study, a 33% to 50% cost ~SPONSE ~D SURVIVAL ~ PATIENTS savings occurred when chemotherapy (such as RECEIVING CHEMOT~E~P~ FOR NON-S~LL cisplatin) was given on an out-patient as opposed to CELL LUNG CANCER. inpatient basis (J Epid 1988). In the current study *RJ Gralla, PJ Hollen, S Eberley, C we looked at costs rather than charges or Cox. Ochsner Cancer Institute, New collections to compare which of two out-patient Orleans, LA; Northeastern University, approaches (home care or clinic) was the least Boston, MA; University of Rochester, expensive. The major cost elements were: personnel Rochester, NY. USA (treating and support staff), drugs and supplies, The importance of evaluation of quality of life (QL) and overhead (space and utilities). We examined two in cancer clinical trials has been emphasized by supportive care measures (blood transfusion and many investigators and organizations. Prognostic amphotericin), and three chemotherapy treatments (of factors for various malignancies are now identified, 379

but the impact of quality of life at baseline has Eight patients had i+ edema or effusions, which not been prospectively evaluated using an instrument cleared despite continued docetaxel administration. with demonstrated psychometrics in lung cancer. We We conclude that prophylactic use of dexamethasone on analyzed a randomized trial of 673 patients with the schedule employed is effective in lessening stage III and IV non-small cell lung cancer who were docetaxel-related fluid retention in patients with also tested with the LCSS quality of life lung cancer, even when docetaxel is given for a year. instrument. The study was conducted at 30 centers in North America, and patients were randomly assigned to receive mitomycin + vinblastine with or without edatrexate. Patient Characteristics: Median KPS=80%; Median age=61; Stage III:IV=19%:81%; 160 RELEVANCE OF RISK FACTORS FOR Males=68%; Median QL score=25 (O=best, lO0=worst). FUNGAL INFECTIONS IN NEUTROPENIC Evaluation was prospectively conducted for PATIENTS traditional endpoints (response and survival) as Montillo M, Corvatta L, OJ~dani M, ^Manso E, Leoni P well as for quality of life; additionally, analysis Clinica di Eraatologia dell'Universitd e ^Sezione di of the impact of prognostic factors was performed Microbiologia - Ospedale Torrette - Ancona using the Cox proportional hazards model and likelihood ratio tests. Results with known Fungal infections are an increasing cause of morbidity and mortality in prognostic factors and other parameters are listed granulocytopenic patients; therefore several methods, either prophylaxis or below: specific antifuagal therapy, have been investigated. The aims of the present RESPONSE EVALUATION: SURVIVAL EVALUATION: study were: 1) to establish the incidence of mycoses and the importance of PARAMETER ODDS RATIO P PARAMETER HAZARD RATIO the several risk factors studied in a group of patients with acute myeloid TREATMENT 1.68 0.01 TREATMENT 0.98 NS leukemia; 2) to evaluate the possible correlation between the colonization of KPS (~80) 1.80 0.03 KPS (<80) 1.89 <0.0001 mucosal surfaces and the following development of invasive fungal infection. GENDER (F) 1.58 0.04 GENDER (M) 1.44 <0.0001 From January 1991 to December 1994, 89 episodes of ncutropenia were AGE (~60) >i.0 0.06 AGE (<60) 1.04 0.69 studied in 51 patients (M/F=32/19; median age 54, range 16-74) receiving QL (better) 1.84 0.02 QL (poorer) 1.70 <0.0001 intensive chemotherapeutic regimens. The median duration of neutropenia The results indicate that quality of life at was 2i.6 d (range 3-67) with neutrophil (PMN') count <0.5 x 109/I and 15.7 baseline not only predicts for the likelihood of d (range 2-67) with PMN count <0.1 x 109/1. We also considered the response and for survival, but also has greater following risk factors: insertion of central venous catheters, mucosytis, total impact than most known prognostic factors. We parenteral nutrition, corticosteroid therapy, administration of broad-spectrum conclude that i) quality of life is a significant antibiotics for a period >7 d. The prophylaxis was conducted with flucomzole factor in lung cancer trials, and that 2) the LCSS (150 rag/d) in 52 episodes and with itraconazole (300 mg/die) in the other 37. instrument has predictive validity in this setting. The overall fungal infections were 19 classified as follows: 16 pulmonary aspergillosis (7 proven, 4 highly probable, 3 probable, 2 suspected), 2 candidiasis (1 C. tropicalis, 1 C. krusei) and 1 fusariosis, The univariate analysis showed a significant correlation between the onset of fungal infection and: a PMN count < 0.5 x 109/1 (p---0.0220), a PMN count <0.1 x ~O* PREVENTION OF CHEMOTHERAPY-INDUCED FLUID 109/1 (p=0.0005) and the positivity of one or more surveillance coltures I%~4J RETENTION: THE EFFICACY OF CORTICO- (p--0.00143). With regard to the other risk factors considered, we did not STEROIDS WITH DOCETAXEL. observe any significant correlation; neveahless fungal infections occurred in *CN Rittenberg, RJ Gralla, JT Cole, CB the 63.2~ of neutropenia episodes with concomitant steroid treatment vs Marques. Ochsner Cancer Institute 17.1% without steroid treatment (p=03657) and in 24% with prolonged New Orleans, Louisiana USA antibiotic therapy vs 7.1% without antibiotics (p---0.28548). The multivariate Prevention of chemotherapy-induced side effects analysis by using stepwise re mession confirmed the PMN count <0.1 x represents a major area of advancement in supportive 109/1 (p=0.0034) and the colonization (p=0.0187) as the most predictive care. Effective antiemetics, antibiotics, and parameters affecting the development of a fungal infection. In our study no methods to lessen leukopenia or nephrotoxicity have difference appeared between the two kinds of prophylaxis regarding the made chemotherapy administration safer and more incidence of both colonization and infection. The median duration of comfortable for patients, while allowing greater cytotoxic dose-intensity. The new taxoid, docetaxel, neutropenin (PMN count <0.t x 109/I) was 21 d in the cases of infective is effective in a variety of malignancies; however, episode vs 12.5 d when no fungal infection was suspected or documented in phase I and II trials dose-limiting edema and (p--O.00005). Mycoses occurred in older patients (median age 60 vs 51 years). effusions associated with cumulative docetaxel In conclusion our study confirmed the importance of both duration and depth (Taxotere, TXT) administration have been reported in of neutropenia. Moreover we pointed out the role of microbiological up to 50% of patients. The mechanism of this surveillance as strong support to opportune terapeutic options. toxicity remains unclear, but it does not appear to be similar to the hypersensitivity widely reported with paclitaxel. We prospectively evaluated 30 patients with non-small cell lung cancer receiving their initial chemotherapy with docetaxel + cisplatin TOPICAL APPLICATION OF MILTEFOSINE (MIL) IN to test the efficacy of dexamethasone in preventing 161 PATIENTS(PTS) WITH SKIN METASTASES. fluid retention. Patient characteristics: median *Vittorio Ferrari,M.D., Federir Lonardi, KPS=80%; males=67%; median age=61. Docetaxel was M.D. Giovanni Pavanato,M.D.,Giorgio Bonoiarelli, given at 75-85 mg/M2 every 3 weeks and cisplatin was M.D., Antonio Jirillo, given at 75-100 mg/M2 on days i, 22, and then every M.D.Dipartlmento di Terapie Oncologiche Integrate, 6 weeks. When docetaxel was given, dexamethasone 8 ULSS 21 37045 Legnago (VR) Italy mg orally bid for 3 days was started 1 day prior to chemotherapy; when both drugs were given, the steroid was given for 4 days (as above) and continued for 2 Mil (MIItex-ASTA) is recently 6ynthetic developed phospholipid further days at 4 mg bid. i+ fluid retention was defined as being asymptomatic and not requiring derivative which belongee to a new therapeutic class of cytostatic medical intervention. No patient experienced > i+ fluid retention. Results: agents related to ether lipid group wiht antitumor activity. NUMBER OF NUMBER OF % WITH >i+ 95% CONFIDENCE PATIENTS TXT DOSES RETENTION INTERVAL A 6% eolution of Mil suitable for topical application has good 25 > 1 0 0% - 9% looal tollerance and mlnimal systemic toxicity. In our departement ii > 6 0 0% - 18% 7 > I0 0 1% - 25% from 4/94 to 12/94 we treated 4 extensively pre-treated pts for 380

skin metastases as palliative care. Malignant cutaneous metastases side effects were dry skin, desquamation, exfoliation. 3 pts with were skin lesion of breast cancer in 3 pts and melanoma in 1, all cutaneous metastases of breast cancer received good palliation of pts had more 70 yrs and they have passed rm/itiple prlor therapies pain and good local control of metastasis for many weeks (2-12)

(surgery, radiotherapy, endocrine and/or chemotherapy).These pts after the end of therapy ; pt with skin lesion of mela/Ioma were treated from 2 to 16 weeks owing to progrelsion, achieving a obtained an suddenly objective response, but after 2 week of relevant remission of local pain .Mil w-as applied with 2 drops/cm2 applications nodules became larger. Probably Mil is an important daily during first week, then twice daily, with modulation in treatment in heavy treated pts withought systemic side effecta relation with individual tolerability. The more important local which could modify the quality of life of pts.