WORLDWIDE ACTIVITY AND SAFETY OF BICALUTAMIDE - A SUMMARY REVIEW

Objectives. To evaluate bicalutamide as a therapy in nearly 3000 patie nts with advanced prostate cancer and to determine the dose-ranging, p harmacodynamic, and pharmacokinetic properties of bicalutamide. To eva luate bicalutamide as a monotherapy or in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy. Results. Bicalut amide is a potent, nonsteroidal antiandrogen with a plasma half-life c onsistent with a once-daily schedule. Monotherapy trials with 50 mg of bicalutamide established its intrinsic activity, as demonstrated by s ubjective and objective responses and decreases in PSA concentrations. In comparison with castration, 50 mg of bicalutamide monotherapy was inferior with respect to survival. In a randomized, double-blind (for antiandrogen therapy) trial, with a median follow-up of 49 weeks, 50 m g of bicalutamide plus an LH RH-A was superior (P = 0.005) to flutamid e plus an LHRH-A in delaying time-to-treatment failure and was better tolerated, as was evident from a significantly (P<0.001) lower inciden ce of diarrhea and fewer withdrawals for adverse events among bicaluta mide-treated patients. With longer follow-up and a 34% mortality, surv ival was equivalent between groups. Dose-related effects of bicalutami de on serum PSA concentrations were clearly demonstrated in the clinic al trial program. With a total exposure of >2800 patient-years, bicalu tamide has been shown to be a well-tolerated therapy with a low incide nce of treatment-related withdrawals. Conclusions. Bicalutamide is a n ew antiandrogen that offers the convenience of once-daily administrati on, demonstrated activity in prostate cancer, and an excellent safety profile. Because it is effective and offers better tolerability than f lutamide, bicalutamide represents a valid first choice for antiandroge n therapy in combination with castration for the treatment of patients with advanced prostate cancer.