Enzalutamide (Xtandi®) for patients with progressive castration-resistant prostate cancer previously treated with docetaxel-based chemotherapy

摘要

Metastatic castration-resistant prostate cancer (mCRPC) poses a major clinical challenge although treatment options have improved over the last years. Enzalutamide is an oral second generation androgen receptor (AR) inhibitor reducing prostate cell proliferation and prostate specific antigen (PSA) levels by targeting multiple steps in the AR signalling pathway. For patients with mCRPC who experience disease progression after initial therapy with docetaxel the U.S. Food and Drug Administration (FDA) licensed enzalutamide in August 2012. In a phase III trial, enzalutamide was compared to placebo in 1,199 docetaxel-refractory patients. The primary endpoint was overall survival (OS). Secondary endpoints included radiographic progression-free survival, time to PSA progression or quality of life. For patients treated with enzalutamide OS was extended by 4.8 months. All secondary endpoints were also improved in the intervention group. Besides cabazitaxel and abiraterone acetate, enzalutamide is the third agent for mCRPC patients previously treated with docetaxel-based chemotherapy. Differences in administration (enzalutamide and abiraterone acetate are taken orally while cabazitaxel is administered intravenously) may influence therapy decisions, but further clinical trials comparing these active agents with each other, and not with placebo are needed.