Degarelix: GnRH receptor antagonist approved for the treatment of advanced prostate cancer

Degarelix is a gonadotropin-releasing hormone (GnRH) receptor antagonist that binds reversibly to the pituitary GnRH receptors; this action decreases the release of gonadotropins and testosterone. This agent was approved on December 24, 2008, for the treatment of patients with advanced prostate cancer.

Efficacy. The efficacy of degarelix was assessed in an open-label, multicenter, randomized, parallel-group study. Patients (N=620) were randomized to receive subcutaneous (SC) degarelix at a starting dose of 240 mg (40 mg/mL) followed by monthly doses of 160 mg (40 mg/mL), SC degarelix at a starting dose of 240 mg (40 mg/mL) followed by monthly doses of 80 mg (20 mg/mL), or intramuscular (IM) leuprolide 7.5 mg monthly for 1 year. Serum testosterone levels were measured at screening, on Days 0, 1, 3, 7, 14, and 28 in the first month, and monthly until study end. The median testosterone level at baseline was approximately 400 ng/dL. The primary goal was to evaluate the efficacy of degarelix in achieving and maintaining testosterone suppression to castration levels (≤50 ng/dL) over 1 year. Among patients treated with degarelix, 98.3% (95% CI, 94.8%–99.4%) of patients in the 240/160-mg dose group and 97.2% (95% CI, 93.5%–98.8%) of patients in the 240/80-mg dose group achieved this end point compared with 96.4% (95% CI, 92.5%–98.2%) of patients treated with leuprolide. Testosterone suppression to castration levels occurred more rapidly among degarelix patients, with 96% of degarelix-treated patients achieving this end point by Day 3 compared with 0 leuprolide-treated patients. Prostate-specific antigen (PSA) levels were assessed as a secondary end point. Among patients treated with degarelix, PSA levels were reduced by 64% at 2 weeks after treatment, by 85% after 1 month of treatment, and by 95% after 3 months of treatment; PSA levels remained suppressed throughout the year of treatment.

Safety. Degarelix should not be administered to women who are or who may become pregnant. Long-term androgen therapy has been demonstrated to prolong the QT interval. Healthcare professionals should weigh the benefits of treatment against the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in those taking class IA or III antiarrhythmic medications. Degarelix therapy suppresses the pituitary gonadal system; as such, diagnostic tests of the pituitary gonadotropic and gonadal functions may be affected during and after treatment. The most common adverse events associated with degarelix treatment include injection-site reactions (eg, pain, erythema, swelling, induration), hot flashes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).