A CONTROLLED TRIAL OF BICALUTAMIDE VERSUS FLUTAMIDE, EACH IN COMBINATION WITH LUTEINIZING-HORMONE-RELEASING HORMONE ANALOG THERAPY, IN PATIENTS WITH ADVANCED PROSTATE-CANCER

Objectives. To compare the efficacy and safety of bicalutamide and flu tamide, each used in combination with luteinizing hormone-releasing ho rmone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. Methods. Randomized, double-blind (for an tiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to go serelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days). Results. With a median duration of follow-up of 49 wee ks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for th e flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A g roup were 34% more likely to fail treatment over the given time period , as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. R esults for secondary endpoints (survival, quality of life, and subject ive response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of pat ients in the bicalutamide plus LHRH-A group (P <0.001). Conclusions. I n patients with metastatic prostate cancer, bicalutamide plus LHRH-A i s well tolerated and provides superior efficacy to flutamide plus LHRH -A with respect to time to treatment failure. Assessment of the effect s of these regimens on longer term survival requires additional time f or follow-up.