New data, new paradigms for treating prostate cancer patients--VI: novel hormonal therapy approaches.

Journal Article (Journal Article)

Until the 1980s, testosterone suppression for men with advanced prostate cancer was managed surgically, with bilateral orchiectomy, or medically, with diethylstilbestrol, a drug that was associated with a problematic side effect profile. Beginning in the mid-1980s, the U.S. Food and Drug Administration approved the first luteinizing hormone-releasing hormone agonists, which proved effective for suppressing circulating testosterone levels and led to a significant shift away from surgical castration to medical management during the past 25 years. The luteinizing hormone-releasing hormone agonists resulted in a periodic return of noncastrate testosterone levels once the receptor desensitization attenuated and the effect of androgen agonism resumed. Therefore, the introduction of an androgen receptor antagonist (gonadotropin-releasing hormone antagonist) appeared, conceptually at least, to be a preferable alternative. The first such agent, degarelix, has proved to provide rapid testosterone suppression without the initial testosterone surge associated with luteinizing hormone-releasing hormone agonists. Other new agents in early development include a selective and irreversible inhibitor of CYP17, abiraterone, which has shown success in patients with castration-resistant metastatic prostate cancer, and MDV3100, a novel small molecule that acts as an oral nonsteroidal antiandrogen agent. In sum, these latest agents might lead to a paradigm shift in the treatment of patients with advanced prostate cancer; however, additional studies are required to clarify the many questions that remain regarding the optimal use and sequence of these agents.

Full Text

Duke Authors

Cited Authors

  • Dreicer, R; Bajorin, DF; McLeod, DG; Petrylak, DP; Moul, JW

Published Date

  • November 2011

Published In

Volume / Issue

  • 78 / 5 Suppl

Start / End Page

  • S494 - S498

PubMed ID

  • 22054921

Electronic International Standard Serial Number (EISSN)

  • 1527-9995

Digital Object Identifier (DOI)

  • 10.1016/j.urology.2011.06.058


  • eng

Conference Location

  • United States