Antiandrogens

General information

Antiandrogens include steroids, such as cyproterone acetate, and non-steroidal agents, such as bicalutamide, flutamide, nilutamide, and abiraterone. They have different endocrine effects and therefore different adverse effects [ ]. Cyproterone acetate tends to result in a loss of sexual interest and erectile dysfunction, whereas most men experience this only moderately or not at all during non-steroidal drug treatment. The most common adverse effects of the non-steroidal agents are gynecomastia and breast pain. Although the incidence of these events varies considerably between studies, there is probably no real difference in the incidence of hormonal adverse effects between the three non-steroidal agents. However, there are important differences between them in other respects. Cyproterone acetate has been linked to adverse effects on serum lipids as well as significant, and in some cases fatal, cardiovascular events; it can also have hepatotoxic effects. Nilutamide is associated with delayed adaptation to darkness, alcohol intolerance, and interstitial pneumonitis. Flutamide is associated with a greater risk of serious hepatotoxicity than bicalutamide or nilutamide. Diarrhea is also more likely to occur during therapy with flutamide than the other antiandrogens. In contrast, no specific non-pharmacological complications have been linked to bicalutamide, while diarrhea and abnormal liver function occur less often than with flutamide. Bicalutamide is a useful alternative to castration in men with prostatic cancer, especially since it appears somewhat less likely to cause impotence or loss of libido [ ].

Mason has reviewed the role of antiandrogens in the treatment of prostate cancer, arguing that with earlier initiation of therapy the long-term adverse effects of castration need to provide the standard by which the acceptability of drugs such as bicalutamide is judged [ ]. There is now evidence that bicalutamide confers significant overall survival benefit when used as an adjuvant to radiotherapy in patients with locally advanced disease. However, the survival data for bicalutamide are not as extensive as those available for LHRH agonists. Although they do not appear to have a significant impact on sexual and physical activity, non-steroidal antiandrogens are often associated with gynecomastia and breast pain, and some are associated with diarrhea.

Are all antiandrogen treatments in locally advanced prostate cancer the same [ ]? The most comprehensively investigated and reported antiandrogen is bicalutamide, which produces survival outcomes similar to those observed with castration in patients with locally advanced prostate cancer. In contrast, only limited clinical data are available for the other non-steroidal antiandrogens (flutamide and nilutamide) and the steroidal antiandrogen cyproterone acetate in patients with locally advanced disease. Cyproterone is associated with loss of libido and erectile dysfunction, cardiovascular risk; there have been occasional reports of fatal fulminant hepatitis and hepatocellular carcinoma. Gynecomastia is rare, in contrast to the non-steroidal antiandrogens. There are no direct comparisons between the three non-steroidal antiandrogens in terms of quality of life, but the available evidence suggests that bicalutamide has a more favorable safety and tolerability profile than nilutamide and flutamide. Unlike cyproterone, non-steroidal antiandrogens appear to be better tolerated than castration, allowing patients to maintain sexual activity, physical ability, and bone mineral density; these agents have a higher incidence of gynecomastia and breast pain (mild to moderate in over 90% of cases), but these are complications that can be effectively managed.

Observational studies