EFFECTS OF VITAMIN-A ON SURVIVAL IN PATIENTS WITH CHRONIC MYELOGENOUSLEUKEMIA - A SWOG RANDOMIZED TRIAL

A national cooperative group trial was conducted in 153 patients with chronic myelogenous leukemia (CML) in chronic phase treated with oral pulse busulfan to determine if oral vitamin A can increase the time to blast crisis and enhance survival of patients. Patients diagnosed wit hin 1 year and in the chronic phase of CML were randomized to receive oral pulse busulfan or the alkylator plus continuous oral vitamin A. D istributions of clinical progression and overall survival were estimat ed using the method of Kaplan and Meier. Associations of these endpoin ts with treatment and other patient characteristics were analyzed usin g the proportional hazards regression method of Cox. Both regimes were well tolerated. Patients in the busulfan plus vitamin A arm had somew hat longer durations of clinical progression-free survival (median 46 months) and overall survival (51 months) compared to those in the busu lfan arm (medians 38 and 44 months). However, the differences were not statistically significant (one-tailed P=0.11 for clinical progression -free survival, 0.081 for survival). After adjustment for significant factors identified in an additional exploratory multivariate analysis, risk of clinical progression or death was 53% (P=0.022) greater and r isk of death 60% (P=0.014) greater among busulfan patients. Given the relatively large though nonsignificant difference between treatment ar ms, the limited statistical power of the study, and the likelihood tha t oral vitamin A may not be the most effective means of delivering ret inoid therapy, we conclude that further investigation of retinoids in chronic phase CML is warranted.