r induration), hot flashes, weight increase, and increases in transaminases and gamma-glutamyltransferase. The majority of the adverse reactions were grade 1/2 in severity; grade 3/4 adverse reactions were uncommon. The injection site reactions were transient, with frequencies of 35-44% in the degarelix arms compared to a frequency of <1% in the leuprolide arm. Hepatic laboratory abnormalities were generally reversible, with grade 3 abnormalities in less than 1% of patients. There were no important differences in adverse reactions between the two degarelix arms, except for fewer injection site reactions in the 240/80 mg arm.
The recommended dosing regimen is a starting dose of 240 mg given as two subcutaneous injections of 120 mg each followed by monthly maintenance doses of 80 mg given as a single subcutaneous injection.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at
FDA Approves Degarelix
The U.S. Food and Drug Administration (FDA) has approved degarelix, an injectable gonadotropin-releasing hormone (GnRH) receptor antagonist, indicated for patients with advanced prostate cancer. Potential trade names are still under review with the FDA.
Phase III studies showed that degarelix is at least as effective as leuprolide (Lupron Depot(R)) in sustaining castrate levels or lower of testosterone, and had a statistically significant faster reduction of testosterone. At Day 3 of treatment, 96% of degarelix patients achieved castrate levels of testosterone, compared with zero percent receiving leuprolide. By Day 14, 99% of degarelix patients achieved castrate levels of testosterone, compared with 18% receiving leuprolide.
In the clinical trial, prostate specific antigen (PSA) levels were also monitored as a secondary endpoint. PSA levels were lowered by 64% two weeks after administration of degarelix, 85% after one month, 95% after three months, and remained suppressed throughout the one year of treatment. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline is related to a clinical benefit.
Prostate cancer is known to grow in the presence of testosterone. Suppression of testosterone has been a treatment goal for advanced prostate cancer for many years. Surgical castration was the standard method of reducing testosterone from the 1940s until the mid-1980s when the earliest forms of medical castration, luteinizing hormone releasing hormone (LHRH) agonists, were introduced.
Degarelix is the only GnRH receptor antagonist approved by the FDA for the treatment of hormonally-sensitive advanced prostate cancer. Degarelix achieves medical castration differently than LHRH agonists, specifically by binding reversibly to GnRH receptors on cells in the pituitary gland, quickly reducing the release of gonadotropins and consequently testosterone.
Overall, the most commonly observed adverse reactions during degarelix therapy included injection site reactions (e.g. pain, erythema, swelling or induration), hot flushes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT). 99% of these observed adverse reactions were Grade 1 or 2 (mild to moderate). Specifically relating to the injection site adverse reactions, most were transient, of mild to moderate i |
