BERKELEY, CA (UroToday.com) - Over the previous 11 years, since the US Food and Drug Administration approved the use of docetaxel, a veritable boom of new and evolving agents has transpired beyond the use of androgen deprivation therapy in advanced prostate cancer. However, in the realm of what’s currently available and approved, the sequencing of drugs revolves around the extent of patient symptoms as well as previous chemotherapy exposure, specifically docetaxel. Immunotherapy with dendritic cell-based therapeutic cancer vaccine, sipuleucel-T, has provided additional ammunition to patient care. Radiopharmaceuticals, previously delegated to use in the palliative setting, have been revived with the use of radium-223, which results in fewer toxic effects on adjacent tissue as well as less myelosuppression and a significant improvement in survival. And despite being over 4 years since its approval, cabazitaxel remains the only chemotherapy to show a survival benefit as second-line treatment for patients whose disease has progressed beyond docetaxel.
Nonetheless, targeting of the androgen signaling pathway has come to the forefront using agents such as abiraterone acetate or enzalutamide. The designation of terms such as “pre-docetaxel” and “post-docetaxel” have spawned large randomized controlled trials in which both abiraterone acetate and enzalutamide have been evaluated. For chemotherapy naïve patients, in the Phase III COUGAR 302, abiraterone acetate resulted in a significantly improved radiographic PFS and a strong trend in OS improvement. In the recently published Phase III PREVAIL trial, enzalutamide resulted in a strikingly positive statistical improvement in overall survival.
This review article summarizes the treatment landscape in metastatic castration-resistant prostate cancer and the variety of agents available for use, including abiraterone acetate, cabazitaxel, sipuleucel-T, radium-223, as well as selected emerging agents, and includes a distinct focus on the utilization of enzalutamide, its mechanism of action, and key pivotal trials that brought about its US Food and Drug Administration approval.
- El-Amm J, Aragon-Ching JB. The changing landscape in the treatment of metastatic castration resistant prostate cancer. Ther Adv Med Oncol. 2013;5(1): 25-40
- Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. N Engl J Med. 2010 Jul 29;363(5):411-22
- Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23
- de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010; 376(9747):1147–1154.
- Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138–148
- Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33
Nihar K. Patel, MD and Jeanny B. Aragon-Ching, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Medicine, Division of Hematology and Oncology, George Washington University Medical Center, Washington, DC, USA