Comparison of two schedules of intermediate-dose methotrexate and cytarabine consolidation therapy for childhood B-precursor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: To compare efficacy and toxicity of two schedules of intermediate-dose methotrexate (IDM) and cytarabine (Ara-C) in remission consolidation of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: In 1986, the Pediatric Oncology Group (POG) began a randomized trial to test two schedules of consolidation chemotherapy in children with newly diagnosed B-precursor cell ALL. MTX and Ara-C were given as overlapping 24-hour infusions. The dose and sequence of MTX and Ara-C administration were based on a preclinical model that had demonstrated synergism between these two agents. Two hundred fifteen patients in complete remission were randomized to front-loading consolidation therapy in which six MTX/Ara-C infusions were administered at 3-week intervals from the 7th through the 19th week of therapy. Two hundred thirteen patients in complete remission were randomized to receive standard consolidation therapy in which the six MTX/Ara-C infusions were given every 12 weeks from the 7th through the 67th week of therapy.
RESULTS: Both regimens produced similar rates of adverse side effects, except for a higher incidence of CNS toxicity in individuals randomized to the front-loading arm (32 of 215 v 12 of 213 patients, P = .002). Leukoencephalopathy occurred in three patients on the front-loading regimen and was permanent in one. By Kaplan-Meier analysis, the probability of continuing in complete remission for 5 years was 79% (SE = 5%) and 85% (SE = 5%) for good-risk patients, and 66% (SE = 6%) and 61% (SE = 7%) for poor-risk patients randomized to front-loading and standard regimens, respectively.
CONCLUSION: Although differences in complete remission durations were not statistically significant by log-rank analysis (P = .62 for good-risk patients, .89 for poor-risk patients, and .99 overall), the results are comparable to those in previous studies using more toxic agents as components of remission consolidation therapy.

RCT Entities:   Population Interventions Outcomes