title: New data, new paradigms for treating prostate cancer patients--VI: novel hormonal therapy approaches.
abstract: 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.
authors: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Robert
authors: R
authors: Dreicer
authors: Dean F
authors: DF
authors: Bajorin
authors: David G
authors: DG
authors: McLeod
authors: Daniel P
authors: DP
authors: Petrylak
authors: Judd W
authors: JW
authors: Moul
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors
chemical_list: D059002:Androgen Receptor Antagonists; D007987:Gonadotropin-Releasing Hormone; D013254:Steroid 17-alpha-Hydroxylase