Investigational GnRH blocker shows potential for advanced prostate cancer

March 27, 2008

MILAN (Reuters Health) - The investigational gonadotropin-releasing hormone (GnRH) antagonist degarelix is as effective as standard androgen deprivation therapy in men with prostate cancer, according to phase III results announced at the 23rd Annual Meeting of the European Association of Urology (EAU).

GnRH agonists are the mainstay of androgen deprivation therapy for prostate cancer, but are associated with late onset of testosterone and prostate-specific antigen (PSA) reduction, and an initial hormone surge that increases the risk of tumor stimulation," Dr. Laurent Boccon-Gibod pointed out.

GnRH blockers, on the other hand, induce rapid, profound, and sustained testosterone suppression.

Dr. Boccon-Gibod, professor of urology at CHU Hopital Bichat-Claude Bernard in Paris, and colleagues elsewhere compared the efficacy and safety of degarelix (80 or 160 mg monthly) with that of the GnRH agonist leuprolide depot, 7.5 mg monthly, over 12 months in 610 men with histologically confirmed adenocarcinoma of the prostate in whom androgen ablation was indicated.

In the study, a treatment response was defined as the suppression of testosterone to 0.5 ng/mL or less at monthly measurements from day 28 to day 364.

Results showed that both doses of degarelix were at least as effective as leuprolide in terms of response to treatment.

Degarelix demonstrated a quicker onset of action. That is, at day 3, 97% and 96% of men in the degarelix 160-mg and 80-mg groups, respectively, had testosterone less than or equal to 0.5 ng/ml compared with no patients who received leuprolide.

The experimental drug did not cause a testosterone surge or microsurge, and PSA fell more rapidly with degarelix than with leuprolide.

"The findings clearly suggest that degarelix is a superior androgen deprivation therapy over a GnRH agonist and that the new drug rivals orchidectomy in terms of efficacy but without the adverse psychological outcomes," Mr. John Anderson, consultant urologic surgeon at the Royal Hallamshire Hospital in Sheffield, UK, said in a news conference.

"In fact," he noted, "usually about 80% of men choose medical over surgical castration, and this new agent seems to be a better form of medical castration than the gold standard androgen deprivation therapy."