Abiraterone acetate in the treatment of metastatic castration-resistant prostate cancer: review of the clinical dataAuthor(s): D Schrijvers
Abiraterone acetate (AA), after metabolization to abiraterone, is an oral inhibitor of the cytochrome P450C17 (CYP17) complex. It inhibits the production of androgens by interfering with the enzymes C17α hydroxylase and C17-C20 lyase. It was tested in patients with metastatic castration-resistant prostate cancer and showed promising results in Phase I and II studies with prostate specific antigen and radiological responses. In a randomized Phase III trial, AA in combination with prednisone increased median overall survival compared with prednisone alone in progressive docetaxel-pretreated patients with metastatic castration-resistant prostate cancer. Side effects of AA were mild with urinary tract infections, edema and hypokalemia when used in combination with prednisone. There was an influence on pharmacokinetic parameters in patients with renal and moderate hepatic failure without severe clinical complications and no dose adjustments are necessary. AA is a potent inhibitor of CYP2D6 and CYP1A2, and can interact with the metabolism of other drugs as shown in ‘in vitro’ studies.