Emerging treatment options for patients with castration-resistant prostate cancer

Authors

  • Daniel George,

    Corresponding author
    1. Divisions of Medical Oncology and Urology, Duke University Medical Center, Durham, North Carolina
    • Associate Professor of Medicine and Surgery, Director of Genitourinary Oncology, Divisions of Medical Oncology and Urology, Duke University Medical Center, Durham, NC 27705.
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  • Judd W. Moul

    1. Division of Urology, Department of Surgery, and Duke Prostate Center, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina
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    • Director, Duke Prostate Center, Division Chief.


  • Disclosures: Daniel George, MD, serves as a speaker for Dendreon, Genentech/Roche, Novartis, Pfizer, and Sanofi-Aventis; is a consultant for Astellas, Dendreon, Genentech/Roche, J&J, Medivation, Novartis, Pfizer, and Sanofi-Aventis; and receives research grants from AstraZeneca, Dendreon, GlaxoSmithKline, J&J, Novartis, and Pfizer. Judd W. Moul, MD, serves as a speaker for Sanofi-Aventis, is a consultant for Amgen, AstraZeneca, Bayer, and Medivation, and is a clinical trial investigator for AstraZeneca.

Abstract

BACKGROUND

Most prostate cancer-related deaths occur in patients with castration-resistant prostate cancer (CRPC). Recent preclinical and clinical studies have identified intracellular signaling pathways and changes in the tumor and bone microenvironment as potential key drivers of CRPC. This increased understanding of mechanisms associated with CRPC has driven the development of numerous new agents, many of which are poised to alter the current CRPC treatment landscape.

METHODS

A review of literature was conducted to identify ongoing and planned phase III studies of novel agents to treat CRPC.

RESULTS

Multiple studies were identified, including novel androgen biosynthesis inhibitors (abiraterone, TAK-700), androgen-receptor inhibitors (MDV3100), angiogenesis inhibitors (aflibercept, tasquinimod), endothelin antagonists (zibotentan, atrasentan), a Src tyrosine kinase inhibitor (dasatinib), a novel radiotherapy (radium-223), and new immunotherapies (ipilimumab and ProstVac). In addition, both sipuleucel-T (an immunotherapy) and cabazitaxel (third-generation taxane) and the RANK-L inhibitor, denosumab, have recently been approved by the US Food and Drug Administration.

CONCLUSIONS

Various combinations of these agents could theoretically be used to treat future patients with CRPC by targeting multiple signaling pathways as well as aspects of the tumor and bone microenvironments. Additional research will be needed to understand how to best use these agents and individualize care to optimize CRPC patient outcomes. Prostate 72:338–349, 2012. © 2011 Wiley Periodicals, Inc.

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