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Managing Metastatic Prostate Cancer In Your Urological Oncology Practice pp 215–230Cite as

Sequencing Therapies in Metastatic Castration—Resistant Prostate Cancer

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Abstract

Since 2004, six agents have been approved for men with castration-resistant prostate cancer (CRPC) on the basis of Phase III data indicating a survival advantage with each of these drugs. Two of these agents, abiraterone and enzalutamide, inhibit androgen receptor (AR) signaling as their primary mechanism of action. In addition, taxanes, the only class of chemotherapeutic shown to afford a survival advantage for men with CRPC, may also function to impair AR-signaling through inhibiting microtubule mediated AR nuclear trafficking. Given these overlapping mechanisms of action it is not surprising that clinical evidence of cross-resistance between these AR-directed agents has begun to emerge, and questions regarding the optimal sequence for using each of these drugs persist. It also remains unclear at what point agents with mechanisms of action not directly related to AR function (i.e. sipuleucel-t and radium-233) should be utilized. In this chapter, we will discuss the key issues surrounding the decision-making that goes into choosing one CRPC drug over another; review the biologic basis for cross-resistance between agents; and highlight some of the data in support of clinical cross-resistance between these drugs.

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  1. Department of Medicine, Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, 825 Eastlake Ave E, Seattle, WA, 98109, USA

    Michael T. Schweizer & Bruce Montgomery

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  1. Michael T. Schweizer
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Correspondence to Michael T. Schweizer .

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  1. School of Medicine, Wake Forest University, Winston Salem, North Carolina, USA

    K.C Balaji

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Schweizer, M.T., Montgomery, B. (2016). Sequencing Therapies in Metastatic Castration—Resistant Prostate Cancer. In: Balaji, K. (eds) Managing Metastatic Prostate Cancer In Your Urological Oncology Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-31341-2_13

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  • DOI: https://doi.org/10.1007/978-3-319-31341-2_13

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