A 1-Year, Open Label, Randomized Phase II Dose Finding Study of Degarelix for the Treatment of Prostate Cancer in North America

Purpose

Degarelix is a gonadotropin-releasing hormone receptor antagonist (blocker) with rapid onset of action suppressing gonadotropins, testosterone and prostate specific antigen in prostate cancer. In the present open label, randomized study in North America we evaluated the efficacy and safety of a starting dose of 200 mg degarelix followed by monthly injections of 60 or 80 mg during 1 year of prostate cancer treatment.

Materials and Methods

A total of 127 patients (median age 76 years, range 47 to 93) with histologically confirmed prostate cancer were enrolled in the study. Efficacy was assessed by measuring serum testosterone and prostate specific antigen.

Results

Median baseline testosterone and prostate specific antigen levels were 4.13 ng/ml (P25–P75 3.03–5.11) and 13.4 ng/ml (P25–P75 6.80–25.7), respectively. The starting dose induced a rapid suppression of testosterone in that 88% of the patients had testosterone levels of 0.5 ng/ml or less 1 month after the injection. For patients who had testosterone levels of 0.5 ng/ml or less after 1 month, 93% and 98% of those receiving maintenance doses of 60 and 80 mg, respectively, had testosterone levels that were consistently 0.5 ng/ml or less at all monthly measurements from 1 month to 1 year. No evidence of testosterone surge was detected. In both groups prostate specific antigen decreased by 96% after 1 year and median time to 90% reduction in prostate specific antigen was 56 days. Six patients (5%) withdrew from the study due to adverse events.

Conclusions

Degarelix treatment for 1 year resulted in a fast, profound and sustained suppression of testosterone and prostate specific antigen with no evidence of testosterone surge. Degarelix was well tolerated.

Key Words: prostate, adenocarcinoma, gonadotropin-releasing hormone, prostate-specific antigen, testosterone

Abbreviations and Acronyms: AE, adverse event, ALT, alanine aminotransferase, DHT, dihydrotestosterone, FSH, follicle-stimulating hormone, GnRH, gonadotropin-releasing hormone, ITT, intent to treat, LH, luteinizing hormone, PSA, prostate specific antigen, ULN, upper limit of normal reference range