Novel agents and new therapeutics in castration-resistant prostate cancer

Abstract

This review highlights recent therapeutic advances in systemic therapies for prostate cancer (PCa). Progress in PCa therapeutics has been made during the past year with the approval of a vaccine therapy, second-line chemotherapy, and reported survival advantage for a CYP (17,20) lyase inhibitor in castration-resistant prostate cancer (CRPC). This report will summarize the recently reported and expected data for PCa trials including an evaluation of intermittent vs. continuous androgen deprivation therapy. Denosumab is shown to support bone mineral density in hormonal sensitive PCa patients. Targeting of androgen-dependent pathways in CRPC postchemotherapy has been shown to improve survival with the lyase inhibitor abiraterone, and lead to prostate-specific antigen and objective responses with an androgen receptor antagonist (MDV3100). However, the addition of bevacizumab to docetaxel/prednisone in treating metastatic CRPC failed to provide a survival benefit. Cabazitaxel in metastatic CRPC postdocetaxel did demonstrate a survival benefit. Provenge, an autologous dendritic cell-based vaccine, demonstrated a reduction in the risk of death in metastatic CRPC. Other immunotherapy agents, including Prostvac and ipilimumab are under investigation. We also discuss the receptor tyrosine kinase inhibitor XL184 and poly (ADP-ribose) polymerase inhibitors which are in early clinical trials. Recent advances in androgen targeting, chemotherapy, immunotherapy, and other targeted therapies have led to significant improvements in the care of CRPC patients.