Details

Autor(en) / Beteiligte

• Goodman, Jr, Oscar B

Titel

Is there a role for LHRH antagonists in prostate cancer?

Ist Teil von

• Oncology (Williston Park, N.Y.), 2009-06, Vol.23 (7), p.632, 635-635

Ort / Verlag

United States: Intellisphere, LLC

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• The recent US Food and Drug Ad- ministration (FDA) approval of degarelix, a luteinizing hormone- releasing hormone (LHRH) antagonist, has renewed interest in this class of drugs as a prostate cancer therapy. Approval was based on a prospective phase ?? trial of 610 patients random- ized to one of two dosing schedules of degarelix, or standard-of-care monthly leuprolide acetate monotherapy, with initial antiandrogen therapy allowed at the treating physician's discretion for prevention of clinical flare. [1] The study clearly met its primary endpoint, to demonstrate equivalence of degarelix and leuprolide in suppressing testosterone from 28 to 364 days after initiating therapy. As Crawford and Hou discuss, the primary difference between the two drugs was predictably observed within the first 28 days, in the form of an LHRH agonist-induced testosterone surge not seen with an LHRH antagonist. Crawford and Hou highlight the substantial differences in the downstream biology of LHRH agonists and antagonists. Specifically, LHRH agonists are less effective at suppressing FSH than antagonists, with a surge in LH and FSH followed by a persistence of FSH in patients receiving LHRH agonist therapy at a level 54.8% below baseline vs 89% below baseline in patients receiving degarelix. Notably, however, after 280 days this difference disappeared between the two treatment arms, with FSH levels appearing to slowly rise in degarelix patients. The authors speculate that lower FSH levels could potentially result in decreased osteoclastogenesis and increased bone density, but it remains to be seen whether this is clinically relevant as it was not an endpoint of the phase ?? trial. [1] Interestingly, patients who undergo orchiectomy have 10-fold higher levels of FSH then those receiving LHRH agonists,[8] with evidence of neither increased skeletal events nor reduced efficacy relative to LHRH agonist monotherapy.