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Management of Metastatic Castration-Resistant Prostate Cancer

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Abstract

Metastatic prostate cancer remains a considerable therapeutic challenge; however, advances in clinical research have resulted in five new treatments in the last 2 years. The immunotherapy sipuleucel-T, the cytotoxic cabazitaxel, the androgen biosynthesis inhibitor abiraterone acetate, the radioisotope al-pharadin and the anti-androgen MDV3100 have all been shown to improve overall survival in randomized phase III studies for patients with metastatic castration-resistant prostate cancer. The therapeutic strategies of targeting androgen-receptor signalling and other key intracellular pathways involved in tumour progression and treatment resistance are yielding promising results. Agents such as the dual vascular endothelial growth factor receptor/MET inhibitor cabozantinib, the clusterin inhibitor custirsen and the Src inhibitor dasatinib have shown encouraging results in phase II studies. Novel immunotherapeutics such as prostate-specific membrane antigen-directed therapy and the anti-cytotoxic T lymphocyte-associated receptor 4 (CTLA4) antibody ipilimumab are also under investigation. Optimal methods of treatment selection, combination and sequencing have yet to be determined.

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Acknowledgements

Johann S. de Bono reports being an employee of the Institute of Cancer Research, where abiraterone was first designed and synthesized and which has a commercial interest in abiraterone, and receiving consulting fees from Ortho Biotech Oncology Research and Development (a unit of Cougar Biotechnology), consulting fees and travel support from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dendreon, Enzon, Exelixis, Genentech, GlaxoSmithKline, Medivation, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Supergen, and Takeda, and grant support from AstraZeneca. Andrew Eichholz and Deborah Mukherji report being employees of the Institute of Cancer Research. Dr Mukherji has received lecture fees and travel support from Pfizer and Johnson and Johnson and travel support from Bayer and Sanofi-Aventis.

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Mukherji, D., Eichholz, A. & De Bono, J.S. Management of Metastatic Castration-Resistant Prostate Cancer. Drugs 72, 1011–1028 (2012). https://doi.org/10.2165/11633360-000000000-00000

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