Recent advances in second-line treatment of castration-resistant prostate cancer

Abstract

Patients with metastatic castration-resistant prostate cancer (CRPC) no longer responsive to docetaxel have a poor prognosis, worsened quality-of-life, and traditionally few options for treatment. This review addresses promising and practice-changing developments for the treatment of CRPC in the second-line setting. Recent data for cabazitaxel, a novel taxane chemotherapy, and abiraterone acetate, a novel inhibitor of androgen synthesis, demonstrate significant improvements in the survival of patients with docetaxel-refractory CRPC. We review the mechanisms of action of these agents and data from phase III clinical trials, contextualizing their place in therapy. We also update other areas of investigation, including oral platinum analogues, vascular-endothelial growth factor receptor targeted therapy, inhibitors of chaperone proteins, and androgen receptor antagonists. Upon disease progression after first-line docetaxel chemotherapy, cabazitaxel and abiraterone improve survival of patients with CRPC and are important novel treatment options. Potential toxicity from cabazitaxel necessitates careful patient selection and supportive care. Both abiraterone and cabazitaxel are also being evaluated in the first-line setting, and therefore the optimal sequencing of therapies remains uncertain. Many other novel agents continue to be evaluated and promising classes of agents include antisense oligonucleotides against clusterin (custirsen) and androgen receptor antagonists (MDV3100).