Beyond Taxanes: Novel Therapeutic Strategies for Castration-Resistant Prostate Cancer

Introduction

Prostate cancer is the most frequently diagnosed nonskin cancer in men with approximately 190000 new cases and 27000 deaths annually in the United States. Androgen deprivation has been the backbone of advanced prostate cancer treatment, either with chemical castration (gonadotropin releasing hormone [GnRH] agonists) or surgical castration. Treatment of metastatic prostate cancer is life extending, though palliative, with primary androgen ablation relieving pain and reducing metastatic burden in >95% of patients.

Abstract

BACKGROUND

Prostate cancer is one of the leading causes of cancer mortality among men. The initial success in treating advanced prostate cancer with androgen deprivation is short lived. Historically, there have been few treatment options for castrate-resistant prostate cancer (CRPC). The recent approvals of new treatments for CRPC appear promising.

MATERIALS AND METHODS

A comprehensive review of recently published prospective phase II/III trials of therapeutic options for CRPC was done. Studies that led to FDA approval and high impact phase II studies were selected for inclusion in this review.

RESULTS

The approvals of docetaxel, cabazitaxel, and sipuleucel-T by the FDA for treatment of CRPC have demonstrated survival benefit in advanced CRPC. A number of clinical trials are underway looking at the efficacy of newer androgen pathway inhibitors such as Abiraterone and MDV 3100. Preliminary results suggest that these agents are promising for the treatment of CRPC.

CONCLUSION

The treatment of CRPC has shifted from pure palliation of symptoms to life prolonging therapy. Although the newer agents have improved CRPC survival, there is a continued need to develop better and more effective treatments.

Keywords

castration-resistant prostate cancer, novel therapeutics, second-line chemotherapy, androgen receptor targeted therapy, prostate cancer immunotherapy