Novel agents for the therapy of castration-resistant prostate cancer: Overview of pivotal studies and new strategies to come

Objective. - Recently, new agents have been developed in the treatment of prostate cancer. Our aim was to review phase III studies that involved novel agents in the treatment of castration resistant prostate cancer. Methods. - PubMed databases were searched for original articles published with the search terms: prostate cancer, castration resistant, metastatic, targeted therapy, biologic agents, immunotherapy and clinical trials. Proceedings from 2008 of conferences of the American Society of Clinical Oncology, American Urological Association, and the European Association of Urology were also searched. We included phase III studies that involved: abiraterone, MDV 3100, cabazitaxel, sipuleucel-T, radium-223, and denosumab. Results. - Abiraterone and MDV 3100 are two new hormotherapies that showed an increased overall survival of 15 and 18 months respectively before after docetaxel based chemotherapy in randomized trials. Cabazitaxel became the standard second line chemotherapy after docetaxel. Sipuleucel-T has emerged as the first approved vaccine in prostate cancer. It showed a 22% reduction of mortality and a prolonged survival time of 4.1 months compared to placebo. A radium-223 based metabolic radiotherapy has showed a better overall survival, delayed and reduced skeletal-related events in placebo controlled randomized trials. Denosumab also delayed the first skeletal-related event in a zoledronic acid controlled trial (20.7 versus 17.1 months, P = 0.0002). Moreover, Denosumab delays bone metastases by 4.1 months compared to placebo. Conclusion. - The novel agents that emerged in the treatment of prostate cancer showed an efficacy in placebo controlled trials. They added new tools in the armamentarium of therapies of castration resistant prostate cancer. (C) 2012 Elsevier Masson SAS. All rights reserved.