Diethylstilboestrol versus bicalutamide in hormone refractory prostate carcinoma: a prospective randomized trial.

OBJECTIVE: To compare the efficacy of diethylstilboestrol (DES) with bicalutamide in the treatment of hormone refractory prostate cancer in relation to its effect on prostate-specific antigen (PSA) and survival.
METHODS: Patients on LHRH analogues for prostate carcinoma with evidence of biochemical or clinical progression were randomized into one of the treatment arms (n=58). The first group (group A, n=26) received 1 mg of DES with 75 mg of aspirin per day in addition to the primary hormonal treatment. The second group (group B, n=32) received bicalutamide at a dose of 50 mg/day in addition to the primary treatment. Patients were followed up every 3 months with their PSA being checked and were also monitored for any clinical progression and adverse effects as a result of treatment. Any adverse event occurring after patients were started on treatment was attributed to the drug and patients were clinically assessed at each visit. Failure of treatment was defined as a 50% or greater increase in PSA after commencing treatment. Once randomized, all patients were followed up for survival regardless of failure of second-line hormonal manipulation.
RESULTS: The mean age of the patients was 76.7 years (60-88, SD 7.4) in group A and 76 years (67-86, SD 6.9) in group B. Twelve patients in each group had metastatic disease. The median follow-up periods for both groups were 24 months (range 6-48 in group A, range 3-54 in group B). 65% of the patients in group A (17/26) and 43.5% (14/32) in group B had a fall in their PSA levels (p=0.08, Fisher's exact test) with 23% (6/26) and 31% (10/32) having a >50% response respectively (p=0.34, Fisher's exact test). Mean PSA nadir in those who responded were 20.6 ng/ml (range 1.6-59.4) and 7.41 ng/ml (range 0.1-42.6) in groups A and B respectively. The median duration of response was 9 months (3-18 months) for group A and 12 months (3-18 months) for group B. Seven patients in group A and 6 in group B experienced adverse events. Three of the 7 in the group A experienced cardiovascular related adverse effects (1 congestive cardiac failure, 1 pulmonary embolism and 1 stroke). At the end of the study period, 14 (54%) of group A patients were alive and 12 (46%) were dead. In group B, 15 (47%) were alive, 16 (50%) were dead and 1 (3%) lost to follow-up. At the completion of the study, 3 patients in each group were still on treatment.
CONCLUSION: Low-dose DES and 50 mg of bicalutamide per day are equally effective in hormone refractory prostate carcinoma with respect to biochemical response, although DES has more severe adverse effects. This is a small sample and larger multicentre trials are needed to give us a definite conclusion. Copyright (c) 2005 S. Karger AG, Basel.

RCT Entities:   Population Interventions Outcomes