HIGH-DOSE CHLORAMBUCIL VERSUS BINET MODIFIED CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, AND PREDNISONE REGIMEN IN THE TREATMENT OF PATIENTS WITH ADVANCED B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA - RESULTS OF AN INTERNATIONAL MULTICENTER RANDOMIZED TRIAL

BACKGROUND. In recent years, much attention has been paid to the possi ble efficacy of intensive chemotherapy in the treatment of advanced, p rogressive B-cell chronic lymphocytic leukemia (CLL) patients. For thi s reason, the International Society for Chemo-Immunotherapy, Chronic L ymphocytic Leukemia Cooperative Group, has begun a randomized multicen ter trial comparing Binet's modified cyclophosphamide, doxorubicin, vi ncristine, and prednisone (CHOP) regimen with continuous high dose chl orambucil (HD-CLB). METHODS. During the period January 1987 to May 199 3, 228 previously untreated CLL patients from 7 cooperative institutio ns were randomized to this trial. Advanced and/or progressive disease was defined by high Total Tumor Mass (TTM) score (>9), and/or short do ubling time (DT) (<12 months), and/or bone marrow failure. The respons e to therapy was defined by reduction of the initial TTM score. The en d points of the trial were response rate, survival, and toxicity. RESU LTS. HD-CLB resulted in a higher response rate than CHOP in evaluable cases, with 89.5% overall responses (complete response + partial respo nse) versus 75%, respectively (P < 0.001). At the time of an analysis performed in July 1995 (after a median follow-up period of 37 months), overall survival was also longer in the HD-CLB treatment arm (median survival, 08 months) than in the CHOP treatment arm (median survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the two treatment arms. CONCLUSIONS. The current study showed that HD-CLB is an effective and well-tolerated therapeutic option for patients wit h advanced and/or progressive CLL. Therefore, the authors recommend it s wider use, possibly in comparison with and/or in combination with ne w therapeutic agents, such as purine analogues. (C) 1997 American Canc er Society.