[Inhibitors of androgen and estrogen biosynthesis in castration-resistant prostate cancer]

Abstract

Advanced prostate cancer remains dependent on androgens and signaling through the androgen receptor despite castrate levels of testosterone defined as testosterone levels <1.7 nmol/l. Ketoconazole, a nonspecific inhibitor of androgen synthesis, has been tested in clinical trials and showed clinical activity; however, high doses are needed which are associated with significant sides effects, mainly neurotoxicity, gastrointestinal intolerance, and liver toxicity. Abiraterone acetate is an irreversible inhibitor of two key enzymes of androgen synthesis, 17a-hydroxylase and 17,20-lyase, and has been tested in a randomized phase III study in patients with castration-resistant prostate cancer who progressed after chemotherapy. Abiraterone plus prednisone resulted in a significant overall survival benefit of 4.6 months compared to prednisone alone. Abiraterone was well tolerated, with mostly mild or moderate side effects consistent with secondary mineralocorticoid excess, namely fluid retention, hypokalemia, and hypertension. Abiraterone plus prednisone is considered a new standard therapy option for patients with castration-resistant prostate cancer who progressed after chemotherapy.