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Флударабин в терапии различных вариантов неходжкинских лимфом
Флударабин в терапии различных вариантов неходжкинских лимфом
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Аннотация
В статье подробно изложены литературные данные об использовании флударабина при неходжкинских лимфомах. Показано, что флударабин, особенно в комбинации с другими цитостатическими препаратами, имеет явные преимущества перед химиотерапией (CHOP, CVP). Подчеркивается, что комбинации флударабина с митоксантроном (FM), циклофосфамидом и митоксантроном (FCM) чрезвычайно эффективны при различных гистологических вариантах лимфом, в том числе при лимфоме из клеток зоны мантии.
Дополнение этих комбинаций ритуксимабом (схемы R-FM, FND+R, R-FCM) позволяет существенно снизить число развивающихся в последующем рецидивов, увеличить выживаемость больных и контролировать минимальную остаточную болезнь. В статье представлены результаты собственных исследований оценки эффективности флударабина как в монорежиме, так и в комбинации (FCD, FCM, R-FC, R-FCM) в сравнении с CHOP, CHOEP, R-CHOP. Выявлены преимущества флударабина перед химиотерапией. При фолликулярной лимфоме высокая эффективность отмечена при использовании схемы FCM (полные ремиссии – 40%). Однако наиболее выразительные результаты получены в группе пациентов, получавших программу R-FCM. Общий ответ составил 100%, полная ремиссия – 60%, что в 3 раза выше, чем в группе R-CHOP. Подчеркивается, что схема иммунохимиотерапии R-FCM является стандартом в 1-й линии терапии больных распространенной фолликулярной лимфомой, а также при прогрессировании лимфомы и выявлении факторов неблагоприятного прогноза.
Ключевые слова: неходжкинские лимфомы, флударабин, ритуксимаб, митоксантрон, полная ремиссия, общий ответ, выживаемость.
Key words: non-Hodgkin's lymphomas, fludarabine, rituximab, mitoxantrone, complete remission, general response, survival rate.
Дополнение этих комбинаций ритуксимабом (схемы R-FM, FND+R, R-FCM) позволяет существенно снизить число развивающихся в последующем рецидивов, увеличить выживаемость больных и контролировать минимальную остаточную болезнь. В статье представлены результаты собственных исследований оценки эффективности флударабина как в монорежиме, так и в комбинации (FCD, FCM, R-FC, R-FCM) в сравнении с CHOP, CHOEP, R-CHOP. Выявлены преимущества флударабина перед химиотерапией. При фолликулярной лимфоме высокая эффективность отмечена при использовании схемы FCM (полные ремиссии – 40%). Однако наиболее выразительные результаты получены в группе пациентов, получавших программу R-FCM. Общий ответ составил 100%, полная ремиссия – 60%, что в 3 раза выше, чем в группе R-CHOP. Подчеркивается, что схема иммунохимиотерапии R-FCM является стандартом в 1-й линии терапии больных распространенной фолликулярной лимфомой, а также при прогрессировании лимфомы и выявлении факторов неблагоприятного прогноза.
Ключевые слова: неходжкинские лимфомы, флударабин, ритуксимаб, митоксантрон, полная ремиссия, общий ответ, выживаемость.
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Key words: non-Hodgkin's lymphomas, fludarabine, rituximab, mitoxantrone, complete remission, general response, survival rate.
Полный текст
Список литературы
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2. Гершанович М.Л. Основные принципы лечения неходжкинских лимфом. Практическая Онкология. 2004; 3: 185–92.
3. Бондаренко И.А., Мартиросов А.Р., Зингерман Б.В. и др. Гемобластозы на территории России: распространенность и смертность (1999–2007 гг.). Вестник гематологии. 2010; 2 (6): 18–9.
4. Бакиров Б.А., Варшавский А.В., Бессмельцев С.С. Динамика заболеваемости гемобластозами в республике Башкортостан (1962–2008 гг.). Medline.ru 2011; 12: 511–21.
5. Поддубная И.В. Обоснование лечебной тактики при неходжкинских лимфомах. Современная онкология. 2002; 1: 3–7.
6. Бессмельцев С.С., Абдулкадыров К.М. Место и роль флударабина в терапии больных неходжкинскими лимфомами. Русский медицинский журнал. 2002; 24 (10): 1119–25.
7. Osterman B, Cavallin-Stahl E, Hagberg H et al. High-grade non-Hodgkin's lymphoma stage I. A retrospective study of treatment, outcome and prognostic factors in 213 patients. Acta Oncol 1996; 35: 171–7.
8. Лимфомы: Научно-практическое издание. Под ред. А.М.Гранова и Н.В.Ильина. СПб.: ФГУ «РНЦХТ», 2010.
9. Абдулкадыров К.М., Самускевич И.Г., Бессмельцев С.С. и др. Диагностика и лечение больных неходжкинскими лимфомами низкой степени злокачественности. Пособие для врачей. СПб, 2000.
10. Поддубная И.В. Лечение индолентных неходжкинских лимфом. Практическая Онкология. 2004; 3: 203–8.
11. Czuczman MS, Fallon A, Mohr A et al. Rituximab in combination with CHOP or fludarabine in low-grade lymphoma. Semin Oncol 2002; 29: 36–40.
12. Coiffier B. Fourteen yearsof high-dose CHOP (ACVB regimen): preliminary conclusions about the treatment of aggressive-lymphoma patients. Ann Oncol 1995; 6: 211–7.
13. Itob K, Obtsu T, Fukuda H et al. Randomized phasa II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin’s lymphoma: Japan Clinical Oncology Group Study 9505. Ann Oncol 2002; 10: 1079–86.
14. Hotta N, Shimacura Y, Isbizuka N et al. Randomized phasa III study of standard CHOP (s-CHOP) versus biweekly CHOP (Bi-CHOP) in aggressive non-Hodgkin’s lymphoma: Japan Clinical Oncology Group Study 9809. Abstr. 2271. Proc Amer Soc Clin Oncol 2003; 22: 565.
15. Krol AD, Berenschot HW, Doekharan D et al. Cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy and radiotherapy for stage I intermediate or high grade non-Hodgkin's lymphomas: results of a strategy that adapts radiotherapy dose to the response after chemotherapy. Radiother Oncol 2001; 58: 251–5.
16. Pfreundschuh M, Trümper L, Kloess M et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL Blood 2004; 104: 626–33.
17. Vargo F, Demeter J. Progress in treatment of non-Hodgkin’s lymphomas. Magy Onkol 2001; 45: 45–50.
18. Tondini C, Balzarotti M, Rampinelli I et al. Fludarabine and cladribine in relapsed/refractory low-grade non-Hodgkin’s lymphoma: a phase II randomized study. Ann Oncol 2000; 11: 231–3.
19. Tobinai K, Watanabe T, Ogura M et al. Phase II Study of Oral Fludarabine Phosphate in Relapsed Indolent B-Cell Non-Hodgkin's Lymphoma. J Clin Oncol 2006; 1 (24): 174–80.
20. Caspard H, Bastion Y, Haioun C et al. Phase II trial of fludarabine monophosphate as first-line treatment in patients with advanced follicular lymphoma: a multicenter study by the Groupe d’Etude des Lymphomes de l’Adulte. Clin Oncol 1996; 14: 514–9.
21. Prabhash K, Vikram GS, Nair R et al. Fludarabine in lymphoproliferative malignancies: a single-centre experience. Nat Med J India 2008; 4 (21): 171–8.
22. Thalhammer-Scherrer R, Geissler K, Schwarzinger I et al Fludarabine therapy in Waldenstrom's macroglobulinemia. Ann Hematol 2000; 10 (79): 556–9.
23. Dhodapkar MV, Jacobson JL, Gertz MA et al. Prognostic factors and response to fludarabine therapy in patients with Waldenstrom macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003). Blood 2001; 1 (9): 41–8.
24. Hagenbeek A, Eghbali H, Monfardini S et al. Fludarabine Versus Conventional CVP Chemotherapy in Newly C Diagnosed Patients With Stages III and IV Low-Grade Malignant Non-Hodgkin’s Lymphoma: Preliminary Results From a Prospective, Randomized Phase III Clinical Trial in 381 Patients. Abstr. 1294. Oncology 1999; 31 (13).
25. Hagenbeek A, Eghbali H, Monfardini S et al. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol 2006; 10 (24): 1590–6.
26. Leblond V, Levy V, Maloisel F et al. Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenstrom macroglobulinemia in first relapse or with primary refractory disease. Blood. 2001; 9 (98): 2640–4.
27. Anderson VR, Perry CM. Fludarabine: a review of its use in non-Hodgkin's lymphoma. Drugs 2007; 11 (67): 1633–55.
28. Бессмельцев С.С., Абдулкадыров К.М. Возможности флударабина в терапии больных неходжкинскими лимфомами. Украiнский журнал гематологii та трансфузiологii. 2004; 4: 5–14.
29. Hochster HS, Oken MM, Winter JN et al. Phase I study of fludarabine plus cyclophosphamide in patients with previously untreated low-grade lymphoma: results and long-term follow-up- a report from the Eastern Cooperative Oncology Group. J Clin Oncol 2000; 18: 987–94.
30. Lazzarino M, Orlandi E, Montillo M et al. Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin’s lymphoma. Ann Oncol 1999; 10: 59–64.
31. Tam CS, Wolf MM, Januszewicz HJ et al. Fludarabine and cyclophosphamide using an attenuated dose schedule is a highly effective regimen for patients with indolent lymphoid malignancies. Cancer 2004; 100: 2181–9.
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Авторы
С.С.Бессмельцев, К.М.Абдулкадыров
Российский научно-исследовательский институт гематологии и трансфузиологии, Санкт-Петербург
Российский научно-исследовательский институт гематологии и трансфузиологии, Санкт-Петербург
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