Abiraterone acetate: in metastatic castration-resistant prostate cancer

Abstract

Oral abiraterone acetate, in combination with prednisone/prednisolone, is used to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. Abiraterone acetate was developed to specifically inhibit cytochrome P450 (CYP)17A1, which is an essential enzyme in the biosynthesis of testosterone. In a pivotal phase III trial in patients with metastatic CRPC who have previously received docetaxel-containing chemotherapy, abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily significantly prolonged overall survival compared with placebo plus prednisone. In this trial, abiraterone acetate plus prednisone was significantly more effective than placebo plus prednisone in prolonging the time to prostate-specific antigen (PSA) progression and in prolonging progression-free survival. Significantly more abiraterone acetate plus prednisone recipients than placebo plus prednisone recipients were considered to be responders, when assessed by PSA levels or radiographic imaging. Treatment with abiraterone acetate plus prednisone in the phase III trial was associated with an acceptable tolerability profile, which was generally similar to that of the placebo plus prednisone group. However, adverse events of special interest (e.g. cardiac disorders and liver-function test abnormalities and adverse events resulting from elevated mineralocorticoid levels because of CYP17A1 inhibition [i.e. fluid retention and oedema, hypokalaemia, hypertension]) occurred in significantly more abiraterone acetate plus prednisone than in placebo plus prednisone recipients.