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Sequencing Systemic Therapies in Metastatic CRPC

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Sequencing Systemic Therapies in Metastatic CRPC

Abstract and Introduction

Abstract


Background: Men with prostate cancer will not die of the disease until it progresses to the metastatic castrationresistant stage. At that stage, the median survival is 9 to 30 months.

Methods: Recently approved and emerging treatments for metastatic castration-resistant prostate cancer (mCRPC) were reviewed based on their mechanisms of action, as well as sequencing and combining these treatments with existing options.

Results: Advances in androgen deprivation therapy, immunotherapy, bone-targeted therapy, and chemotherapy have led to approvals of abiraterone acetate, sipuleucel-T, denosumab, and cabazitaxel for the treatment of mCRPC. Despite improvements in patient survival and quality of life, mCRPC remains incurable.

Conclusions: With the emerging new therapies, this is an unprecedented time in treating mCRPC. A better understanding of their mechanisms of action, the genetic makeup of each mCRPC, and the development of new prognostic and predictive biomarkers will help determine sequencing or different combination treatments for each individual patient.

Introduction


Prostate cancer is the most common cancer among North American men, with approximately 238,590 new cases diagnosed and 29,720 deaths expected in 2013 in the United States. Prostate cancer is not deadly until it progresses to the metastatic castrationresistant stage, defined as progressive prostate cancer despite a castrate level of serum testosterone (< 50 ng/dL). Patients with metastatic castration-resistant prostate cancer (mCRPC) have a progressive and morbid disease process, with a median survival of 9 to 30 months. Although the survival period will likely be improved with newly approved and emerging therapies, mCRPC remains an incurable disease. Based on the palliative nature of systemic therapies, the goals of treatment are to improve survival and to maintain patient quality of life with minimum toxicities. In this article, we review newly approved and emerging therapies for mCRPC, dividing them into four strategies: antiandrogen therapy, immunotherapy, cytotoxic chemotherapy, and bone-targeted therapy. We also discuss how to sequence these treatments to maximize survival benefits.

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