MAXIMAL ANDROGEN BLOCKADE FOR PATIENTS WITH METASTATIC PROSTATE-CANCER - OUTCOME OF A CONTROLLED TRIAL OF BICALUTAMIDE VERSUS FLUTAMIDE, EACH IN COMBINATION WITH LUTEINIZING-HORMONE-RELEASING HORMONEANALOGUE THERAPY

Objectives. To review the outcome of therapy with maximal androgen blo ckade and compare the efficacy and safety of bicalutamide and flutamid e, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Sta ge D2) prostate cancer. Methods. Randomized, double-blind (for antiand rogen therapy), multicenter study with a 2 x 2 factorial design. A tot al of 813 patients were allocated 1:1 to bicalutamide (50 mg once dail y) or flutamide (250 mg three times daily), plus 2:1 to goserelin acet ate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days ). Results. At the rime of analysis (median follow-up, 49 weeks), bica lutamide plus LHRH-A was associated with a statistically significant i mprovement in time-to-treatment failure, the primary endpoint when com pared with flutamide plus LHRH-A. The results with longer follow-up (m edian, 95 weeks) support previous findings of an improved time-to-trea tment failure with bicalutamide plus LHRH-A; however, the difference b etween groups was not statistically significant. A treatment failure e ndpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A gro up. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHR H-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting th e definition for equivalence (<1.25). With longer follow-up, overall m ortality was 34%, with equivalent survival between groups: 32% of pati ents in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29 ). The upper one-sided 95% confidence limit for survival was 1.07, mee ting the definition for equivalence (<1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of pa tients in the bicalutamide plus LHRH-A group (P<0.001). Conclusions. I n patients with metastatic prostate cancer, bicalutamide plus LHRH-A i s effective and well tolerated. Because of its efficacy and tolerabili ty profile, together with its convenient once-daily dosing formulation , bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.