Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: Flutamide versus diethylstilbestrol

Purpose: Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone. Therapy with diethylstilbestrol (DES), leuprolide, or bilateral orchiectomy has been reported to be equivalent. DES is the cheapest preparation, but has the potential for serious cardiovascular or thromboembolic complications. Flutamide is a novel antiandrogen with fewer side effects. Patients and Methods: The Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, randomized study to compare the efficacy of flutamide (250 mg three times daily) to DES (1 mg three times daily) as the primary hormonal therapy for patients with stage D2 prostate cancer. Patients were stratified by performance status, disease sites, and history of cardiovascular disease at randomization. Results: Forty-eight patients received DES and 44 flutamide. Patient characteristics were evenly distributed between the two treatments. The overall response rate was similar (DES, 62%; flutamide, 50%), Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3% of patients on DES and in 17.6% on flutamide (P = .051). Other toxicities were similar between the two treatment arms. However, DES produced significantly longer rime to treatment failure (26.4 v 9.7 months, P = .016) and longer survival than flutamide (43.2 v 28.5 months, P = .040). Conclusion: As the primary hormonal therapy for stage D2 prostate cancer, DES caused more serious cardiovascular or thromboembolic complications than flutamide, Despite this, flutamide was not as active an initial agent as DES. However, the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined, and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies. (C) 1996 by American Society of Clinical Oncology.