Bicalutamide dosages used in the treatment of prostate cancer

BACKGROUND. Androgen deprivation is often used for the treatment of patient s with prostate cancer. Androgen deprivation can be achieved by surgical ca stration or medical castration, with or without using an antiandrogen. Each of these treatments may be used alone, or an antiandrogen may be used alon gside castration to produce combined androgen blockade therapy. METHODS. The nonsteroidal antiandrogen, bicalutamide (Casodex(R)), has been evaluated as a component in combined androgen blockade and as monotherapy. We review the arguments that indicate why a 50-mg once-daily dose of bical utamide is appropriate in combined androgen blockade, while ongoing clinica l trials evaluate 150-mg once-daily as monotherapy in the treatment of pros tate cancer. RESULTS. The choice of the 50-mg dose of bicalutamide when used in combined androgen blockade is supported by four main arguments. First, bicalutamide 50 mg is at least equivalent to, if not better than, flutamide 750 mg in t erms of receptor affinity, potency, and favorable plasma concentration prof ile. Second, the reduction in testosterone concentrations produced by medic al or surgical castration decreases the potential competition between bical utamide and testosterone for androgen receptors in prostate cells, allowing the use of a lower dose of antiandrogen in combined androgen blockade than is necessary in monotherapy. Third, bicalutamide 50 mg has an excellent to lerability profile. Fourth, at the 50-mg dose, bicalutamide plus luteinizin g hormone-releasing hormone analogue was equivalent to flutamide plus lutei nizing hormone-releasing hormone analogue, although there was a trend towar ds longer survival with bicalutamide. Furthermore, investigations of higher doses of bicalutamide have justified evaluation of bicalutamide 150 mg as monotherapy. First, pharmacodynamic studies reveal an increasing prostate-s pecific antigen response with increasing dose, which appears to plateau at a dose of around 150-200 mg. Second, in an analysis with 31% mortality, bic alutamide 150 mg appeared to have equivalent efficacy compared with castrat ion in terms of survival in patients with nonmetastatic prostate cancer. CONCLUSIONS. On the basis of available data, bicalutamide 50 mg is an appro priate dose to use in combined androgen blockade, while 150 mg is being eva luated in ongoing clinical trials as a suitable dose for monotherapy. (C) 1 999 Wiley-Liss, Inc.