Tolerability of Antiandrogens in the Treatment of Prostate Cancer

Abstract

This article presents and discusses data on the tolerability of the antiandrogens, both steroidal (cyproterone acetate; CPA) and non-steroidal (bicalutamide, flutamide, nilutamide), across all stages of hormone-responsive prostate cancer. Steroidal and non-steroidal antiandrogens have different endocrine effects and therefore different pharmacological side effects during monotherapy, with CPA generally resulting in loss of sexual interest and erectile dysfunction, whereas the majority of men retain some sexual interest and function during non-steroidal antiandrogen monotherapy. The most common side effects of the non-steroidal agents are gynaecomastia and breast pain. Although the incidence of these events varies considerably between studies, there is no evidence that there is a true difference in incidence between the three non-steroidal agents. Important differences exist between the antiandrogens with respect to non-pharmacological side effects. CPA has been linked to adverse changes in serum lipids as well as significant, and in some cases fatal, cardiovascular events. CPA can also cause hepatotoxicity. 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. Diarrhoea 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 diarrhoea and abnormal liver function occur less frequently than with flutamide. Thus, when considering antiandrogen therapy at any stage of prostate cancer, bicalutamide appears to have advantages over the other antiandrogens.