Approaches to minimize castration in the treatment of advanced prostate cancer

作者：Zejnullahu Kreshnik; Arevalo Maria G; Ryan Charles J; Aggarwal Rahul

来源：Urologic Oncology-Seminars and Original Investigations, 2016, 34(8): 368-374.

DOI：10.1016/j.urolonc.2016.02.001

• Biochemically recurrent prostate cancer
• Androgen deprivation therapy
• Peripheral androgen blockade

Background: Androgen deprivation therapy (ADT) remains the cornerstone of primary systemic treatment for men with metastatic disease and is a commonly applied therapy in the biochemically relapsed setting. Despite the high response rate with ADT, resistance is universal. Furthermore, over the past decade, there has been a growing appreciation for the significant short-term and long-term toxicities of continuous ADT (CADT). The rationale to develop alternative androgen receptor (AR) targeting strategies that seek to minimize or eliminate the need for upfront castration therapy is 2-fold-(1) delay the emergence of AR-independent disease, potentially improving long-term disease outcomes and (2) mitigate the short-term and long-term side effects of CADT, improving quality of life and potentially lessening comorbidities related to ADT including osteoporosis, diabetes, and potentially cardiovascular disease. The 2 most rigorously studied alternatives to CADT include intermittent ADT and peripheral androgen blockade with the use of first-generation or second-generation AR antagonists. Both intermittent ADT and peripheral androgen blockade have been evaluated in the biochemically relapsed and metastatic setting in multiple phase 2 and 3 studies.
Aim: In the current review, we aim to discuss the data from these studies, as well as the emerging noncastrating strategies.

• 出版日期2016-8