Abiraterone and Increased Survival in Metastatic Prostate Cancer

Abstract

BACKGROUND Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. METHODS We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. RESULTS After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate–prednisone group than in the placebo–prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate–prednisone group than in the placebo–prednisone group. CONCLUSIONS The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.)

Nomogram for Overall Survival of Japanese Patients with Bone Metastatic Prostate Cancer

“…In the United States and in Europe, some new effective agents for CRPC have been approved such as docetaxel, cabazitaxel, sipuleucel-T, abiraterone, and MDV3100 (enzalutmide) [6][7][8][9][10][11]. Unfortunately, treatment for CRPC is very limited in Japan even though docetaxel has been approved [12].…”

Second-line hormonal therapy with the enzalutamid in patients with castrate-resistant prostate cancer

“…Одним из первых гормональных препаратов 2-й линии терапии явился препарат абиратерона ацетат, продемонстрировавший свою эффективность в иссле-дованиях III фазы у пациентов как до, так и после про-веденной химиотерапии доцетакселом [10,11]. Абира-терон -препарат, направленный на ингибирование фермента CYP17, являющегося одним из коэнзимов цитохрома P450.…”

Revisiting the Role of Antiandrogen Strategies in Ovarian Cancer

“…Downstream of this reaction, it further suppresses the generation of estrogens and androgens [71]. The drug is well tolerated and it has been shown to have significant activity in patients with castrate-resistant prostate cancer, leading to a recently reported randomized phase III trial that provided positive evidence of the drug's efficacy in this disease [72]. Because the steroid hormones upstream of aromatase and downstream of CYP17 could be important in the activation of ARs and possibly other nuclear steroid hormone receptors in EOC growth, abiraterone may impact EOC cell proliferation and survival by its androgen-suppressing activity.…”