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.