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Overview of the latest treatments for castration-resistant prostate cancer

Nature Reviews Urology volume 10, pages 522–528 (2013)Cite this article

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Abstract

Over the past few years, we have developed an increased understanding of the molecular mechanisms that underlie prostate cancer progression and castration resistance and expanded our repertoire of therapeutic options for castration-resistant prostate cancer (CRPC). Four new agents (cabazitaxel, abiraterone acetate, enzalutamide, and radium-233) have been shown to prolong overall survival in patients with CRPC in the postchemotherapy setting. Targeting the androgen receptor pathway continues to have an important role in the treatment of CRPC, with abiraterone acetate and enzalutamide being the most exciting developments. Cabazitaxel is now considered the standard-of-care second-line chemotherapy for men with metastatic CRPC (mCRPC). Bone-targeted therapy is an active area of research, with denosumab being the first bone-targeted agent able to significantly delay the appearance of bone metastases in patients with CRPC and radium-223 being the first radiopharmaceutical agent to improve survival in patients with mCRPC.

Key Points

  • The androgen receptor (AR) pathway remains a therapeutic target in patients with castration-resistant prostate cancer (CRPC)

  • Abiraterone acetate, a selective CYP17 inhibitor, has been approved by the FDA for the treatment of patients with metastatic CRPC (mCRPC) in prechemotherapy and postchemotherapy settings

  • Enzalutamide (formerly known as MDV3100) is a multilevel AR inhibitor that has gained FDA approval for the treatment of patients with mCRPC who have already received docetaxel therapy

  • Cabazitaxel, a taxane-based chemotherapeutic agent, is FDA-approved for patients who progress on, or after, docetaxel regimens

  • Denosumab was the first osteoclast-targeted agent shown to significantly delay bone metastasis in patients with nonmetastatic CRPC

  • Radium-223 was the first radiopharmaceutical agent shown to improve survival in patients with mCRPC

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Figure 1: Emerging therapies for metastatic castration-resistant prostate cancer.

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  1. Centre de Recherche, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke East, Montréal, H2L 4M1, QC, Canada

    Mohamed Bishr

  2. Urology Division, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke East, Montréal, H2L 4M1, QC, Canada

    Fred Saad

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M. Bishr researched the literature for this Review. Both authors wrote, edited, discussed, and reviewed the manuscript prior to submission.

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Correspondence to Fred Saad.

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F. Saad has been paid for consultancy and research by Astellas, Janssen, Sanofi, Amgen, Novartis, and Bayer. M. Bishr declares no competing interests.

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Bishr, M., Saad, F. Overview of the latest treatments for castration-resistant prostate cancer. Nat Rev Urol 10, 522–528 (2013). https://doi.org/10.1038/nrurol.2013.137

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