Combination chemotherapy study for remission maintenance in ALL: an evaluation of vincristine, cyclophosphamide and vincristine, cyclophosphamide, and BCNU: a Southwest Oncology Group Phase II Study.

Vincristine (VCR), cyclophosphamide (CP), and BCNU have antineoplastic activity in acute lymphocytic leukemia. In animal tumor systems, and in a clinical controlled study, vincristine and cyclophosphamide have been demonstrated to be more effective when given sequentially. In animal models, cyclophosphamide and BCNU have a synergistic effect if given simultaneously. In order to evaluate this potentially synergistic schedule in man, children with ALL in their second or greater remission were randomized to receive either a standard vincristine cyclophosphamide regimen (VCR 2 mg/m2 on day 1 and CP 450 mg/m2 on days 2 and 3) or this same regimen with the addition of 50 mg of BCNU given with the CP given on days 2 and 3. The standard two-drug regimen was given every 3 weeks and the potentially synergistic combination was given on a 4-week schedule. The median duration of remission (MDR) for the 18 children receiving the two-drug combination was 13.5 weeks, and for the 20 children receiving the potentially synergistic three-drug regimen combination, 15 weeks. With 95% confidence, the population MDR for the two-drug combination is from 63% to 125% of the population with the three-drug regimen. The toxicities of both regimens was tolerable. No statistically significant synergistic benefit was demonstrated in these patients with the addition of BCNU to cyclophosphamide.