Androgen antagonists: Potential role in prostate cancer prevention

This article summarizes discussions of the importance of androgens and androgen antagonists in the genesis of prostate cancer. These discussions occurred at a recent symposium on prostate cancer chemoprevention sponsored by the National Cancer Institute. Considerable information exists indicating the importance of androgens in the development of prostate cancer. Trials in breast cancer indicate that estrogen antagonists prevent breast cancer-suggesting, by analogy, that the blockade of androgen action might prevent the emergence of prostate cancer. The 5alpha-reductase inhibitors block the intracellular metabolism of testosterone and inhibit the growth of the prostate. Limited data suggest that 5alpha-reductase inhibitors reduces prostate-specific antigen in men with localized and advanced, primary or recurrent prostate cancer. An ongoing national trial of 18,000 men over 50 years of age has completed accrual and will evaluate whether a standard dose of finasteride will prevent the development of prostate cancer. The toxicity profile of finasteride (Proscar, Merck & Co., West Point, PA), the only approved 5alpha-reductase inhibitor, is favorable leading to its evaluation as a potential chemopreventive agent for prostate cancer. Anti-androgens such as bicalutamide (Casodex, AstraZeneca, Wilmington, DE) are active in the treatment of prostate cancer and comparable, in some trials, to testicular androgen suppression. These data suggest that antiandrogens may be active in the prevention of prostate cancer; however, the toxicity of antiandrogens (gynecomastia, gastrointestinal toxicity) poses concerns for application in prevention studies. Opportunities for study of factors predictive or associated with the development of prostate cancer and new agents that may interrupt this process offer numerous leads that may reduce the incidence of prostate cancer.