DOCSLIB.ORG

©Ferrata Storti Foundation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
©Ferrata Storti Foundation Malignant Lymphomas Ifosfamide, epirubicin and etoposide (IEV) regimen as salvage and research paper mobilizing therapy for haematologica 2002; 87:816-821 relapsed/refractory lymphoma http://www.haematologica.ws/2002_08/816.htm patients PIER LUIGI ZINZANI, MONICA TANI, ANNA LIA MOLINARI,* VITTORIO STEFONI, ELIANA ZUFFA,* LAPO ALINARI, ANNALISA GABRIELE, FRANCESCA BONIFAZI, Institute of Hematology and Medical Oncology PATRIZIA ALBERTINI, MARZIA SALVUCCI,* SANTE TURA, “L. e A. Seràgnoli”, University of Bologna; MICHELE BACCARANI *Division of Hematology, Ravenna Hospital, Ravenna, Italy Background and Objectives. Therapy for relapsed/refrac- lthough advanced stage Hodgkin’s disease tory lymphomas should be based only on drugs not (HD) and some aggressive non-Hodgkin’s included in the front-line chemotherapy regimens. We Alymphomas (NHL) are potentially curable adopted the strategy of using salvage chemotherapy to with standard chemotherapy, many patients either debulk disease and simultaneously mobilize stem cells, relapse or never achieve remission.1,2 One way of using a regimen based on ifosfamide and etoposide, improving this situation could be to intensify (drugs not usually used for front-line treatment). front-line chemotherapy, either by dose-escala- tion of conventional therapy3 or by adding high- Design and Methods. A three-drug combination of ifos- famide, epirubicin and etoposide (IEV) was used to treat dose chemotherapy with peripheral blood stem cell 4,5 62 patients with relapsing or refractory aggressive non- (PBSC) rescue. Whereas treatment of relapsing Hodgkin’s lymphoma (NHL; n=51) or Hodgkin’s disease disease with conventional chemo- and/or radiation (HD; n=11). Forty-five of the patients were studied for the therapy is unsatisfactory, especially in those feasibility of peripheral blood stem cell (PBSC) harvest. patients who have had an early relapse,6,7 high- dose chemotherapy and stem cell rescue may Results. The overall and complete response (CR) rates improve prognosis.8,9 Although high-dose chemo- were, respectively, 77% and 32% in the NHL subset and therapy can also be effective as a salvage strate- 81% and 45% in the HD subset. Among the 17 patients gy for HD patients who do not respond to induc- who achieved CR after IEV but did not have a subsequent tion treatment,10 the approach fails with many transplantation, the median duration of the response was 11 9 months (range, 2 to 14 months). Mobilization was suc- refractory primary lymphomas. So, despite our cessful in 33 of 45 (71%) patients. Among the 45 who current ability to cure almost half of all aggressive proceeded to autotransplantation, 27 (60%) were in CR NHL and the majority of HD, effective second-line status after the autograft; 23/45 (51%) patients are cur- therapies are needed for both resistant and relaps- rently in continuous CR with a median follow-up of 25 ing disease. These second-line therapies could months (range, 10-68 months); the relapse-free survival serve both for re-induction prior to high-dose curve shows 83% in this state at 60 months. Twenty- chemotherapy with PBSC rescue, and for patients three (37%) patients are currently in continuous CR with who are not candidates for transplantation. a median follow-up of 25 months. Clinical and hemato- Ideally, second-line therapy should not share any logic toxic effects were mild. mechanism of action or toxicity with the initial induction regimen. In pratical terms, since most Interpretation and Conclusions. Our results indicate the efficacy of the IEV regimen in inducing a good remission primary induction chemotherapy regimens contain rate. IEV is a predictable and highly effective mobilization anthracyclines and tend to be myelosuppressive, regimen in relapsed/refractory patients with aggressive second-line combinations that avoid cardiac tox- NHL or HD. icity and excessive stem cell damage would be par- ©2002, Ferrata Storti Foundation ticularly useful. In multiple trials in which combi- nation chemotherapy has been used to treat Key words: IEV regimen, HD, aggressive NHL, relapsed lymphoma patients following treatment relapse/refractory patients, PBSC mobilization. with CHOP, most of the regimens have included cisplatin, methotrexate, mitoxantrone, and ifos- 12-14 Correspondence: Pier Luigi Zinzani, M.D., Istituto di Ematologia famide. The MINE (ifosfamide, mitoxantrone, e Oncologia Medica “L. e A. Seràgnoli”, Policlinico S.Orsola, etoposide) regimen was one of the first to include via Massarenti 9, 40138 Bologna, Italy. Phone: international +39.051.6363680. Fax: international ifosfamide, and several investigators have used +39.051.6364037. E-mail: [email protected] variants of this combination to treat patients with haematologica vol. 87(8):august 2002 IEV regimen in pretreated lymphomas 817 relapsed lymphomas.15-23 All these studies have stage II to IV according to the Ann Arbor staging indicated that ifosfamide-based regimens incor- system;25 Eastern Cooperative Oncology Group porating etoposide and other agents can induce (ECOG)26 performance status less than 3; human responses in transplanted patients and, when used immunodeficiency virus negativity; and normal in high doses in combination with growth factors, renal, hepatic, and cardiac functions [including a can act as excellent mobilizers of PBSC. baseline resting left ventricular ejection fraction We previously reported20 on the use of IEV (ifos- (LVEF) greater than 50%]. In all cases, staging eval- famide, epirubicin, and etoposide) alone in a group uation included initial hematologic and chemical of resistant or relapsing lymphoma (HD and aggres- surveys, in addition to chest X-rays, abdominal sive NHL) patients. Herein, we report an extended ultrasonography, computed tomography of the follow-up of a larger series of patients treated with chest and abdomen, and bone marrow biopsy. Oth- IEV either alone or prior to autologous bone mar- er studies included lymphography (in 2 HD row transplantation (ABMT). patients), and liver biopsy when appropriate. No patient underwent staging laparotomy. Bulky Design and Methods disease was defined as a tumor mass ≥6 cm. Twen- ty-three patients had stage II, 15 had stage III, and Patients’ characteristics 24 had stage IV disease. Twenty-two patients pre- The present study regards 62 consecutive, previ- sented bulky disease. Thirty-eight patients had ele- ously treated patients (37 males, 25 females; medi- vated serum lactate dehydrogenase (LDH) level and an age, 42 years, range 14-62) with either NHL 29 patients had at least an extranodal involvement. (n=51) or HD (n=11) diagnosed between January The performance status was 0-1 in 40 patients 1995 and September 2000 (Table 1). and 2 in the remaining 22 patients; according to Eligibility criteria included a confirmed histolog- the stage, 5 patients had stage II, 29 stage III, and ic diagnosis of aggressive or indolent NHL or HD 28 stage IV disease. Histologically, all 51 NHL according to the REAL classification;24 disease patients had aggressive disease. Informed consent was always provided according to the Declaration Table 1. Patients’ characteristics [n=62]. of Helsinki. Treatment protocol Age (years) Median 42 The IEV schedule was as follows: ifosfamide Range 14-62 2,500 mg/m2/day i.v. over 4 hours followed by mes- 2 Sex M/F 37/25 na (3 g/m ) and hydration over 10 h. daily to pro- tect against urothelial toxicity on day 1 to 3, epiru- Histology bicin 100 mg/m2 i.v. on day 1; etoposide 150 mg/m2 Hodgkin’s disease 11 Follicular grade III 3 i.v. on days 1 to 3. Courses were repeated every 21 Peripheral T-cell 2 days, with a target total of three courses; chemo- Diffuse large B-cell 44 therapy was given in an outpatient setting. In the Anaplastic large B-cell 2 45 patients for whom PBSC harvest was feasible only 2 conditioning courses were given in order to Response status at time of treatment: reduce tumor volume before high-dose chemother- PR 12 Relapse 33 apy and PBSC reinfusion. For these patients, sub- Refractory 17 cutaneous administration of granulocyte colony- stimulating factor (G-CSF) (5 g/kg, once daily) Elevated LDH level Yes 38 µ No 24 was commenced on day 6 and continued until completion of the PBSC harvest. The remaining 17 Performance status 0-1 40 222 patients, who were considered unsuitable for mye- loablative therapy, all received 3-4 cycles; G-CSF Extranodal sites Yes 29 was administered at the same dose from day 6 to No 33 14 of each cycle. Stage II 5 Response III 29 IV 28 All patients were restaged after completion of IEV chemotherapy. Clinical and pathologic evalua- IPI 0-2 45 tions were made by repeating radiographic inves- 317 ≥ tigations and bone marrow and/or liver biopsies haematologica vol. 87(8) august 2002 818 P.L. Zinzani et al. whenever previous results had been positive. Com- Table 2. Responses according to disease status prior to IEV plete response (CR) and partial remission (PR) were therapy of all 62 patients. defined according to international criteria.27 No response (NR) was anything less than PR. Standard HD (n=11) NHL (n=51) response response ECOG toxicity criteria were used.26 Statistical methods Disease status No. pts CR PR NR CR PR NR Overall survival was measured from the time of at time of treatment entry into the protocol until death; the relapse- During PR 12 3 1 0 2 3 .3 free interval was calculated from the date of response after autograft until relapse or death; Relapsed 33 2 1 0 12 18 0 event-free survival was measured from the auto- Refractory 17 0 2 2 2 2 9 graft to the first event (resistance to treatment, relapse, death, last follow-up). Overall, relapse-free survival, and event-free survival curves were cal- culated according to the method of Kaplan and PR (a good PR; GPR). Among the patients treated Meier.28 Deaths from lymphoma, secondary to lym- with IEV after relapse, 14 (43%) achieved CR and phoma treatment or to any disease (related or 19 (57%) PR.
Load more

Recommended publications
  • Hodgkin Lymphoma Treatment Regimens
    HODGKIN LYMPHOMA TREATMENT REGIMENS (Part 1 of 5) Clinical Trials: The National Comprehensive Cancer Network recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. Classical Hodgkin Lymphoma1 Note: All recommendations are Category 2A unless otherwise indicated. Primary Treatment Stage IA, IIA Favorable (No Bulky Disease, <3 Sites of Disease, ESR <50, and No E-lesions) REGIMEN DOSING Doxorubicin + Bleomycin + Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + Vinblastine + Dacarbazine vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over (ABVD) (Category 1)2-5 60 minutes.
    [Show full text]
  • (Rituxan®), Rituximab-Abbs (Truxima®), Rituximab-Pvvr (Ruxience®) Prior Authorization Drug Coverage Policy
    1 Rituximab Products: Rituximab (Rituxan®), Rituximab-abbs (Truxima®), Rituximab-pvvr (Ruxience®) Prior Authorization Drug Coverage Policy Effective Date: 2/1/2021 Revision Date: n/a Review Date: 7/2/20 Lines of Business: Commercial Policy type: Prior Authorization This Drug Coverage Policy provides parameters for the coverage of rituximab (Rituxan®), rituximab-abbs (Truxima®), and rituximab-pvvr (Ruxience®). Consideration of medically necessary indications are based upon U.S. Food and Drug Administration (FDA) indications, recommended uses within the Centers of Medicare & Medicaid Services (CMS) five recognized compendia, including the National Comprehensive Cancer Network (NCCN) Drugs & Biologics Compendium (Category 1 or 2A recommendations), and peer-reviewed scientific literature eligible for coverage according to the CMS, Medicare Benefit Policy Manual, Chapter 15, section 50.4.5 titled, “Off- Label Use of Anti-Cancer Drugs and Biologics.” This policy evaluates whether the drug therapy is proven to be effective based on published evidence-based medicine. Drug Description1-3 Rituximab (Rituxan®), rituximab-abbs (Truxima®), and rituximab-pvvr (Ruxience®) are monoclonal antibodies that target the CD20 antigen expressed on the surface of pre-B and mature B- lymphocytes. Upon binding to cluster of differentiation (CD) 20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production.
    [Show full text]
  • Effectiveness of Rituximab-Containing Treatment Regimens in Idiopathic Multicentric Castleman Disease
    Annals of Hematology https://doi.org/10.1007/s00277-018-3347-0 ORIGINAL ARTICLE Effectiveness of rituximab-containing treatment regimens in idiopathic multicentric Castleman disease Yujun Dong1 & Lu Zhang2 & Lin Nong 3 & Lihong Wang1 & Zeyin Liang1 & Daobin Zhou2 & David C. Fajgenbaum4 & Hanyun Ren1 & Jian Li2 Received: 27 February 2018 /Accepted: 23 April 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Human herpes virus type 8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disease often involving constitutional symptoms, cytopenias, and multiple organ system dysfunction. In China, the majority of MCD cases are HHV-8 negative. Given that siltuximab, the only FDA-approved treatment for iMCD is not available in China; rituximab- and cyclophosphamide-containing regimens are often used in the treatment of Chinese iMCD patients. To evaluate the efficacy of rituximab in this rare and heterogeneous disease, clinical and pathological data from 27 cases of iMCD were retrospectively analyzed from two large medical centers in China. The novel diagnostic criteria for iMCD were applied, and POEMS syndrome, IgG4-related diseases, and follicular dendritic cell sarcomas cases were excluded from analyses. Total response rate of rituximab- and cyclophosphamide-containing regimens was 55.5%, with 33.3% (9/27) of the cases reaching CR and 22.2% (6/27) PR. In the 14 cases of R-R iMCD, total response rate was only 42.9% (CR 14.3% [2/14], PR 28.6% [4/14]). The 5-year OS of these 27 iMCD cases was 81% (95% CI 64–98; 27 total patients, 4 events, 23 censored) after receiving these regimens, but the 5-year PFS was 43% (95% CI 19–66; 25 total patients, 11 events, 14 censored).
    [Show full text]
  • PET Predicts Prognosis After 1 Cycle of Chemotherapy in Aggressive Lymphoma and Hodgkin’S Disease
    PET Predicts Prognosis After 1 Cycle of Chemotherapy in Aggressive Lymphoma and Hodgkin’s Disease Lale Kostakoglu, MD1; Morton Coleman, MD2; John P. Leonard, MD2; Ichiei Kuji, MD1; Holly Zoe1; and Stanley J. Goldsmith, MD1 1Division of Nuclear Medicine, Department of Radiology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York; and 2Center for Lymphoma and Myeloma, Division of Hematology and Oncology, Department of Medicine, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York Early identification of chemotherapy-refractory lymphoma patients Accurate evaluation of response to therapy is of vital provides a basis for alternative treatment strategies. Metabolic imag- importance in the management of patients with lymphoma 18 ing with F-FDG PET offers functional tissue characterization that is (1). The main endpoint of chemotherapy is the achievement useful for assessing response to therapy. Our objective was to deter- mine the predictive value of 18F-FDG PET early during chemotherapy of complete remission, which is associated with a longer (after 1 cycle) and at the completion of chemotherapy for subsequent progression-free survival (PFS) and potential cure than is progression-free survival (PFS) in patients with aggressive non- partial remission (2). The definition of complete remission, Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD). Methods: however, is usually based on anatomic imaging modalities 18F-FDG PET (dual-head coincidence camera with attenuation cor- that may be unable to differentiate viable tumor from post- rection) was performed before and after 1 cycle of chemotherapy on therapy changes such as scarring or fibrosis.
    [Show full text]
  • High-Dose Mitoxantrone + Melphalan (MITO/L-PAM)
    Leukemia (2001) 15, 256–263 2001 Nature Publishing Group All rights reserved 0887-6924/01 $15.00 www.nature.com/leu High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: high tolerability with reversible cardiotoxicity C Tarella1, F Zallio1, D Caracciolo1, A Cuttica1, P Corradini1,2, P Gavarotti1, M Ladetto1, V Podio3, A Sargiotto4, G Rossi5, AM Gianni6 and A Pileri1 1Dipartimento di Medicina e Oncologia Sperimentale, Divisione Universitaria di Ematologia; Serv. 3Univ. e 4Osped di Medicina Nucleare; 5Divisione Universitaria di Radioterapia-Azienda Ospedaliera S Giovanni Battista di Torino, Torino; and 6Unita` Trapianto Midollo, Ist Naz. Tumori, Milano, Italy Hematological and extrahematological toxicity of high-dose The ease deriving from the excellent tolerability of PBPC (hd) mitoxantrone (MITO) and melphalan (L-PAM) as condition- procedures probably slowed down the efforts aimed to look ing regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at dis- for innovative and possibly more effective conditioning regi- ease onset). Autograft was the final part of a hd-sequential mens. In fact, most autograft programs employed nowadays (HDS) chemotherapy program, including a debulkying phase are based on conditioning regimens designed several years (1–2 APO ± 2 DHAP courses) and then sequential adminis- ago, such as TBI + cyclophosphamide (CY), or regimens con- tration of hd-cyclophosphamide, methotrexate (or Ara-C) and taining nitrosurea or melphalan (L-PAM), such as BEAM, CBV etoposide, at 10 to 30 day intervals. Autograft phase included: or BEAC.17–21 Looking for a better conditioning regimen, one (1) hd-MITO, given at 60 mg/m2 on day −5; (2) hd-L-PAM, given at 180 mg/m2 on day −2; (3) PBPC autograft, with a median of should not only consider the antitumor activity of a given drug 11 × 106 CD341/kg, or 70 × 104 CFU-GM/kg, on day 0.
    [Show full text]
  • Ifosfamide and Etoposide-Based Chemotherapy As Salvage and Mobilizing Regimens for Poor Prognosis Lymphoma
    Bone Marrow Transplantation, (1999) 23, 413–419 1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http://www.stockton-press.co.uk/bmt Ifosfamide and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma J Mayer1, Z Korˇ´ıstek1,IVa´sˇova´1, J Vorlι´cˇek1 and P Vodva´rˇka2 1Department of Internal Medicine – Hematooncology, Masaryk University Hospital, Brno; and 2Department of Radiotherapeutic Medicine, Faculty Hospital, Ostrava, Czech Republic Summary: Growth factors (G-CSF or GM-CSF, granulocyte or gra- nulocyte–macrophage colony-stimulating factors) and/or a We treated 40 patients with poor prognosis lymphomas. higher dose of cyclophosphamide are standard for adequate Patients with non-Hodgkin’s lymphoma (NHL, n = 14) mobilization of PBSC, although other combinations of received MINE chemotherapy (mesna, ifosfamide polychemotherapy and growth factors can be used. A com- 1330 mg/m2 and etoposide 65 mg/m2 by i.v. infusions on bination of chemotherapy and growth factors is more effec- days 1–3, mitoxantrone 8 mg/m2 i.v. on day 1), and those tive than growth factors and chemotherapy alone and inten- with Hodgkin’s disease (HD, n = 26) received VIM sity of chemotherapy correlates with the degree of PBSC chemotherapy (mesna, ifosfamide 1200 mg/m2 by i.v. mobilization.3–8 In lymphoma patients, PBSC can be mobil- infusion on days 1–5, etoposide 90 mg/m2 by i.v. infusion ized with growth factors alone or by a combination of high- on days 1, 3 and 5, and methotrexate 30 mg/m2 i.v. on dose cyclophosphamide and growth factors, but these regi- days 1 and 5).
    [Show full text]
  • Acronyms for Oncology Regimens
    ACRONYMS AND ABBREVIATIONS OF COMMONLY USED REGIMENS ACRONYM CHEMOTHERAPY COMBINATION 7 + 3 Anthracycline (daunorubicin/idarubicin) or anthracenedione (mitoxantrone)/cytarabine ABV Doxorubicin/ bleomycin/vincristine ABVD Doxorubicin/ bleomycin/vinblastine/dacarbazine AC Doxorubicin/cyclophosphamide ACE Doxorubicin/cyclophosphamide/etoposide AI Doxorubicin/ifosfamide AIDA Tretinoin/idarubicin/dexamethasone/mitoxantrone/6-mercaptopurine/ methotrexate AP Doxorubicin/cisplatin AT Doxorubicin/docetaxel BEACOPP Bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/ prednisone BEP Bleomycin/etoposide/cisplatin BMC Bleomycin/methotrexate/carmustine CAD Cyclophosphamide/doxorubicin/dacarbazine CAP Cyclophosphamide/doxorubicin/cisplatin CAPIRI Capecitabine/irinotecan CAPOX Capecitabine/oxaliplatin CAV Cyclophosphamide/doxorubicin/vincristine CDE Cyclophosphamide/doxorubicin/etoposide CDE-R Cyclophsopahmide/doxorubicin/etoposide/rituximab CECA Cyclophosphamide/etoposide/carboplatin/cytarabine CFAR Alemtuzumab/fludarabine/cyclophosphamide/rituximab CHOEP Cyclophosphamide/doxorubicin/vincristine/etoposide/prednisone CHOP Cyclophosphamide/doxorubicin/vincristine/prednisone CHOP-R Cyclophosphamide/doxorubicin/vincristine/prednisone/rtuximab ChlVPP Chlorambucil/vinblastine/procarbazine/prednisone CMF Cyclophosphamide/methotrexate/5-Fluorouracil CNOP Cyclophosphamide/mitoxantrone/vincristine/prednisone CODOX-M Cyclophsopahmide/vincristine/doxorubicin/cyclophosphamide/methotrexate/ leucovorin/intrathecal cytarabine/intrathecal methotrexate
    [Show full text]
  • United States Patent (19) 11 Patent Number: 6,048,849 Hausheer Et Al
    US006048849A United States Patent (19) 11 Patent Number: 6,048,849 Hausheer et al. (45) Date of Patent: Apr. 11, 2000 54) FORMULATIONS AND METHODS OF Brock, Norbert, et al., Studies on the Urotoxicity of Oxaza REDUCING TOXCITY OF phosphorine Cytostatics and its Prevention-III. Profile of ANTINEOPLASTICAGENTS Action of Sodium 2-mercaptoethane Sulfonate (Mesna). Eur. J. Cancer Clin. Oncol., 18(12): 1377–1387, 1982. 75 Inventors: Frederick H. Hausheer; Thomas J. Brock, Von N., et al., Arzneim Forsch 32: 486-487 (1982). Dodd, both of Boerne, Tex. Brock, N., et al., Pharmacokinetcis and Mechanism of Action of Detoxifying Low-Molecular-Weight Thiols. J. 73 Assignee: BioNumerik Pharmaceuticals, Inc., Cancer Res. Clin. Oncol., 108: 87–97, 1984. San Antonio, TeX. Brock, Norbert, et al., The development of mesna for regional detoxification. Cancer Treatment Reviews, 21 Appl. No.: 09/225,700 10(Suppl. A): 33–43, 1983. 22 Filed: Jan. 6, 1999 Burkert, Hans, et al., Clinical Overview of meSna. Cancer Treatment Reviews, 10(Suppl. A): 175-181,1983. Related U.S. Application Data Burkert, H., et al., Bioavailability of Orally Administered Mesna. Arzneim.-Forsch/Drug Res., 34:(II), 1597–1600, 60 Division of application No. 08/954,678, Oct. 17, 1997, Pat. 1984. No. 5,919,816, which is a continuation-in-part of application No. 08/553,005, Nov. 3, 1995, Pat. No. 5,902,610, which is Campbell, A. Bruce, et al., Plasma Platinum Levels: Rela a continuation-in-part of application No. 08/338,379, Nov. tionship to Cisplatin Dose and Nephrotoxicity. Cancer Treat 14, 1994, Pat.
    [Show full text]
  • Managing Relapsed and Refractory DLBCL
    Managing relapsed and refractory DLBCL Andy Davies [email protected] Oxford Lymphoma Course June 2018 DLBCL is a curable disease Overall survival: All randomised 83.0% 82.0% HR=0.907 p=0.549 Real World Data Haematological Malignancies research Network 2017 Events occur early… Overall survival from Overall survival from diagnosis 2 years event free Maurer M J et al. JCO 2014;32:1066-1073 Outcomes of R-CHOP population 100% 90% 15-25% refractory 80% 5% PR patients 70% 20-30% relapses 60% 50% 40% 50-60% cured 30% 20% 10% 0% Coiffier and Sarkozy et al 2016 How can we identify those patients that may not respond well…? IPI Age greater than 60 years Stage III or IV disease Elevated serum LDH ECOG > 2 More than 1 extranodal site Age adjusted IPI Stage LDH Performance status Ziepert at al. J Clin Oncol 28:2373-2380. Primary Refractory Early relapse Late relapse Not eligible for HDT • Age Eligible for HDT • Co-morbidity consolidation • No response to reinduction • No stem cells at harvest Reinduction regimen Reinduction regimen (I hate ‘salvage’) Followed by HDT+PBSCT Primary Refractory Early relapse Late relapse Not eligible for HDT • Age Eligible for HDT • Co-morbidity consolidation • No response to reinduction • No stem cells at harvest Reinduction regimen Reinduction regimen (I hate ‘salvage’) Followed by HDT+PBSCT PARMA Trail (Phillip NEJM 1995) • PARMA study (n=215 aggressive relapsed disease) • 109 demonstrated chemosenstivity after DHAP x2: randomised DHAP x4 more or BEAC + ABMT • OS 53 vs 32% at 5 years (P=0.038) • Time to relapse (< or > 12 months most important prognostic factor, along with second line aaIPI and response to salvage PR vs CR Guglielmi et al, JCO 1998 PARMA TRIAL: ABMT vs DHAP (A) Actuarial PFS curves in responding early relapses (less than 12 months from initial diagnosis) according to treatment arm (ABMT versus DHAP).
    [Show full text]
  • High-Grade Non-Hodgkin Lymphoma
    High-grade non-Hodgkin lymphoma High-grade non-Hodgkin lymphoma Diffuse large B-cell lymphoma Burkitt lymphoma Double-hit and triple-hit lymphoma Central nervous system lymphoma Other high-grade B-cell lymphomas T-cell lymphomas This book has been researched and written for you by Lymphoma Action, the only UK charity dedicated to people affected by lymphoma. We could not continue to support you, your clinical team and the wider lymphoma community, without the generous donations of our incredible supporters. As an organisation we do not receive any government or NHS funding and so every penny received is truly valued. To make a donation towards our work, please visit lymphoma-action.org.uk/Donate 2 Your lymphoma type and stage Your treatment Key contact Name: Role: Contact details: Job title/role Name and contact details GP Consultant haematologist/ oncologist Clinical nurse specialist or key worker 3 About this book High-grade (or aggressive) non-Hodgkin lymphoma is a type of blood cancer that develops from white blood cells called lymphocytes. It is a broad term that includes lots of different types of lymphoma. This book explains what high-grade non-Hodgkin lymphoma is and how it is diagnosed and treated. It includes tips on coping with treatment and day-to-day life. The book is split into chapters. You can dip in and out of it and read the sections that are relevant to you at any given time. Important and summary points are written in the chapter colour. Lists practical tips and chapter summaries. Gives space for questions and notes.
    [Show full text]
  • Proposal for the Inclusion of Mesna (Sodium 2-Mercaptoethane Sulfonate)
    17th Expert Committee on the Selection and Use of Essential Medicines Geneva, 2009 Proposal for the inclusion of mesna (sodium 2-mercaptoethane sulfonate) for the prevention of ifosfamide and cyclophosphamide (oxazaphosphorine cytotoxics) induced haemorrhagic cystitis FINAL REPORT Paul A. Carless BHSc, MMedSc.(Clin.Epid) Discipline of Clinical Pharmacology School of Medicine and Public Health Faculty of Health University of Newcastle Level 5, Clinical Sciences Building, NM2 Newcastle Mater Hospital Edith Street, Waratah, 2298 New South Wales AUSTRALIA Tel +61-02-49211726 Fax + 61-02-49602088 WHO EML - Final Report - MESNA (sodium 2-mercaptoethane sulfonate) – February 2008 1. Summary statement of the proposal Mesna is proposed for the inclusion in the World Health Organisation (WHO) Model List of Essential Medicines for the prevention of oxazaphosphorine-induced (ifosfamide and cyclophosphamide) hemorrhagic cystitis. 2. Name of focal point in WHO submitting or supporting the application 3. Name of the organisation(s) consulted and/or supporting the application Discipline of Clinical Pharmacology, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Level 5, Clinical Sciences Building, NM2, Newcastle Mater Hospital, Edith Street, Waratah, 2298, New South Wales, Australia. 4. International Nonpropriety Name (INN, generic name) of the medicine Mesna (Chemical name: sodium 2-mercaptoethane sulfonate). 5. Formulation proposed for inclusion Tablets: 400 mg, 600 mg Injection: 400 mg / 4 ml, 1g / 10 ml 6. International availability – sources, if possible manufactures (Appendix A) Mesna is marketed under 14 different trade names in 32 countries worldwide. A detailed list of manufacturers and distributors is presented in Appendix A. 7. Whether listing is requested as an individual medicine or as an example of a therapeutic group Listing is requested on the Model List of Essential Medicines as an individual medicine.
    [Show full text]
  • DNA Topoisomerases of Kinetoplastid Parasites: Brief Overview and Recent Perspectives
    Curr. Issues Mol. Biol. (2019) 31: 45-62. caister.com/cimb DNA Topoisomerases of Kinetoplastid Parasites: Brief Overview and Recent Perspectives Sourav Saha†, Somenath Roy Chowdhury† and Hemanta K. Majumder* Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India. *Correspondence: [email protected], [email protected] †Both authors contributed equally. t DOI: https://dx.doi.org/10.21775/cimb.031.045 Abstract nucleic acid metabolic processes, permanent or Topoisomerases are a group of enzymes that resolve temporary separations of DNA strands cause dif- DNA topological problems and aid in diferent ferent topological constraints. Tese topological DNA transaction processes viz. replication, tran- constraints, if not removed, become disastrous and scription, recombination, etc. inside cells. Tese greatly afect cellular health (Chen et al., 2013). proteins accomplish their feats by steps of DNA DNA topoisomerases are the molecular machines strand(s) scission, strand passage or rotation and inside all kinds of living cells that resolve these subsequent rejoining activities. Topoisomerases of kinds of topological tensions. Not only that, DNA kinetoplastid parasites have been extensively stud- topoisomerases sometimes introduce measured ied because of their unusual features. Te unique topological tensions in the double helical DNA presence of heterodimeric Type IB topoisomerase molecules to aid DNA transaction processes and prokaryotic ‘TopA homologue’ Type IA topoi- (Champoux, 2001). somerase in kinetoplastids still generates immense Te mechanism of action of DNA topoisomer- interest among scientists. Moreover, because of ases involves following major steps: (1) binding of their structural dissimilarity with the host enzymes, topoisomerase to the substrate DNA, (2) cleavage topoisomerases of kinetoplastid parasites are atrac- by trans-esterifcation reaction accompanied by tive targets for chemotherapeutic interventions to the formation of a transient phosphodiester bond kill these deadly parasites.
    [Show full text]