[en] We conducted a randomized trial to compare the intensive conventional chemotherapy regimen ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with poor-risk aggressive lymphoma. Patients aged 61 to 69 years who had aggressive non-Hodgkin lymphoma with at least one prognostic factor of the age-adjusted international prognostic index (IPI) were included. ACVBP consisted of an induction phase of intensified chemotherapy and central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. Of the 708 patients registered for the study, 635 were eligible. The rate of complete response was 58% in the ACVBP group and 56% in the CHOP group (P =.5). Treatment-related death occurred in 13% of the ACVBP group and 7% of the CHOP group (P =.014). At 5 years, the event-free survival was 39% in the ACVBP group and 29% in the CHOP group (P =.005). The overall survival was significantly longer for patients treated with ACVBP, at 5 years it was 46% compared with 38% for patients treated with CHOP (P =.036). CNS progressions or relapses were more frequent in the CHOP group (P =.004). Despite higher toxicity, the ACVBP regimen, used as first-line treatment for patients with poor-risk aggressive lymphoma, is superior to standard CHOP with regard to both event-free survival and overall survival. (C) 2003 by The American Society of Hematology.
Disciplines :
Hematology
Author, co-author :
Tilly, Hervé
Lepage, Eric
Coiffier, Bertrand
Blanc, Michel
Herbrecht, Raoul
Bosly, André
Attal, Michel
Fillet, Georges ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale
Guettier, Catherine
Jo Molina, Thierry
Gisselbrecht, Christian
Reyes, Félix
Language :
English
Title :
Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma
Publication date :
2003
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
Devesa SS, Fears T. Non-Hodgkin's lymphoma time trends: United States and international data. Cancer Res. 1992;52(suppl 19):5432-5440.
Varterasian ML, Graff JJ, Severson RK, Weiss L, Al-Katib AM, Kalemkerian GP. Non-Hodgkin's lymphoma: an analysis of the Metropolitan detroit SEER database. Cancer Invest. 2000;18:303-308.
Coltman CA, Dahlberg S, Jones SE, et al. CHOP is active in thirty percent of patients with large cell lymphoma: a twelve year Southwest Oncology Group follow up. In: Skarin AT, ed. Advances in Cancer Chemotherapy: Update on Treatment for Diffuse Large Cell Lymphoma. New York, NY: ParkRow; 1986:71-77.
Shipp MA, Harrington DP, Klatt MM, et al. Identification of major prognostic subgroups in patients with large-cell lymphoma treated with m-BACOD or M-BACOD. Ann Intern Med. 1986;104;757-765.
Longo DL, DeVita VT Jr, Duffey PL, et al. Superiority of Pro-MACE-CytaBOM over Pro-MACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized study. J Clin Oncol. 1991;9:25-38.
Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985;102:596-602.
Gordon LI, Harrington D, Andersen J, et al. Comparison of a second-generation chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med. 1992;327:1342-1349.
Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993;328:1002-1006.
Coiffier B, Bryon PA, Ffrench M, et al. Intensive chemotherapy in aggressive lymphoma: updated results of LNH-80 protocol and prognostic factors affecting response and survival. Blood. 1987;70:1394-1399.
Coiffier B, Gisselbrecht C, Herbrecht R, et al. A multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma. J Clin Oncol. 1989;7:1018-1026.
Tilly H, Mounier N, Lederlin P, et al. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. J Clin Oncol. 2000;18:1309-1315.
Haioun C, Lepage E, Gisselbrecht C, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the LNH87-2 protocol. A Groupe d'Etude des Lymphomes de l'Adulte study. J Clin Oncol. 2000;18:3025-3030.
The International Non-Hodgkin's Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329:987-994.
Non-Hodgkin's lymphoma Classification Project: National Cancer Institute sponsored study of classification of non-Hodgkin's lymphoma: summary and description of a working formulation for clinical usage. Cancer. 1982;49:2112-2135.
Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Comittee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17:3835-3849.
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.
Gisselbrecht C, Haioun C, Lepage E, et al. Placebo controlled phase III trial of lenograstim (Glycosylated recombinant human G-CSF) in aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 1997;25:289-300.
Lepage E, Gisselbrecht C, Haioun C, et al. Prognostic significance of received relative dose intensity in non-Hodgkin's lymphoma patients: application to the LNH-87 protocol. Ann Oncol. 1993;4:651-656.
Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphoma. J Clin Oncol. 1999;17:1244-1253.
Freeman DH. Applied categorical data analysis. Vol 79, Statistics text-books and monographs. New York, NY: Marcel Dekker; 1987.
Kaplan EL, Meier P. Non parametric estimation for incomplete observations. J Am Stat Assoc. 1958;53:457-481.
Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163-170.
Cox DR. Regression model and life tables. J R Stat Soc Ser B. 1972;34:187-220.
Gottlieb AJ, Anderson JR, Ginsberg SJ, et al. A randomized comparison of methotrexate dose and the addition of bleomycin to CHOP therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas: Cancer and Leukemia Group B study 7851. Cancer. 1990;66:1888-1896.
Sonneveld P, de Ridder M, van der Lelie M, et al. Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy. J Clin Oncol. 1995;13:2530-2539.
Zinzani PL, Martelli M, Storti S, et al. Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma. Leuk Lymphoma. 1995;19:329-335.
Montserrat E, Garcia-Conde J, Vinolas N, et al. CHOP vs ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphoma: long-term results of a multicenter randomized trial. Eur J Haematol. 1996;57:377-383.
Jerkeman M, Anderson H, Cavallin-Stahl E, et al. CHOP versus MACOP-B in aggressive lymphoma: a Nordic Lymphoma Group randomized trial. Ann Oncol. 1999;10:1079-1086.
Linch DC, Smith P, Hancock BW, et al. A randomized British National lymphoma Investigation trial of CHOP vs a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma. Ann Oncol. 2000;11:87-90.
Wolf M, Matthews JP, Stone J, Cooper IA, Robertson TI, Fox RM, Long-term survival advantage of MACOP-B over CHOP in intermediate-grade non-Hodgkin's lymphoma: the Australian and New Zealand Lymphoma Group. Ann Oncol. 1997;8:71-75.
Morel P, Lepage E, Brice P, et al. Prognosis and treatment of lymphoblastic lymphoma in adults: a report on 80 patients. J Clin Oncol. 1992;10:1078-1085.
Divine M, Lepage E, Briere J, et al. Is the small non-cleaved ceil lymphoma histologic subtype a poor prognostic factor in adults patients? A case-controlled study. J Clin Oncol. 1996;14:240-248.
Kwak LW, Halpern J, Olshen RA, Horning SJ. Prognostic significance of actual dose-intensity in diffuse large-cell lymphoma: results of a tree-structure survival analysis. J Clin Oncol. 1990;8:963-977.
Meyer RM, Hryniuk WM, Goodyear MD. The role of dose intensity in determining outcome in intermediate-grade non-Hodgkin's lymphoma. J Clin Oncol. 1991;9:339-347.
Meyer RM, Quirt IC, Skillings JR, et al. Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1993;329:1770-1776.
Pfreundschuh M, Truemper L, Kloess M, et al. 2-weekly vs. 3-weekly CHOP with and without etoposide for patients >60 years of age with aggressive non-Hodgkin's lymphoma: results of the completed NHL-B2 trial of the DSHNHL [abstract]. Blood. 2002;100:774a.
Treon SP, Chabner BA. Concepts in use of high-dose methotrexate therapy. Clin Chem. 1996;42:1322-1329.
Bosly A, Lepage E, Coiffier C, et al. Outcome is not improved with alternating chemotherapy in aggressive lymphoma: a prospective randomized study from the GELA on 810 patients. Hematol J. 2001;2:279-285.
Van Besien K, Ha CS, Murphy S, et al. Risk factors, treatment and outcome of central nervous system recurrence in adults with intermediate grade and immunoblastic lymphoma. Blood. 1998;91:1178-1184.
Haioun C, Besson C, Lepage E, et al. Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis. Ann Oncol. 2000;11;689-690.
Coiffier B, Lepage E, Herbrecht R, et al. CHOP chemotherapy plus Rituximab compared to CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med. 2002;346:235-242.