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.
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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.
In the current review, we aim to discuss the data from these studies, as well as the emerging noncastrating strategies.
Urologic oncology. 2016 Mar 01 [Epub ahead of print]
Kreshnik Zejnullahu, Maria G Arevalo, Charles J Ryan, Rahul Aggarwal
Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA., Servicio de Oncologia Medica, Hospital Universitario La Paz, Madrid, Spain., Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA., Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA.