The efficacy and safety of degarelix: a 12‐month, comparative, randomized, open‐label, parallel‐group phase III study in patients with prostate cancer

• Published in: BJU international 2008-12, Vol.102 (11), p.1531-1538
• Main Authors: Klotz, Laurence, Boccon‐Gibod, Laurent, Shore, Neal D., Andreou, Cal, Persson, Bo‐Eric, Cantor, Per, Jensen, Jens‐Kristian, Olesen, Tine Kold, Schröder, Fritz H.
• Format: Article
• Language: English
• Subjects: adenocarcinoma; Adenocarcinoma - drug therapy; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; gonadotrophin‐releasing hormone; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gynecology. Andrology. Obstetrics; Humans; Leuprolide - therapeutic use; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Prospective Studies; prostate neoplasm; Prostate-Specific Antigen - metabolism; prostate‐specific antigen; Prostatic Neoplasms - drug therapy; testosterone; Testosterone - metabolism; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2008.08183.x

OBJECTIVE To evaluate the efficacy and safety of degarelix, a new gonadotrophin‐releasing hormone (GnRH) antagonist (blocker), vs leuprolide for achieving and maintaining testosterone suppression in a 1‐year phase III trial involving patients with prostate cancer. PATIENTS AND METHODS In all, 610 patients with adenocarcinoma of the prostate (any stage; median age 72 years; median testosterone 3.93 ng/mL, median prostate‐specific antigen, PSA, level 19.0 ng/mL) were randomized and received study treatment. Androgen‐deprivation therapy was indicated (neoadjuvant hormonal treatment was excluded) according to the investigator’s assessment. Three dosing regimens were evaluated: a starting dose of 240 mg of degarelix subcutaneous (s.c.) for 1 month, followed by s.c. maintenance doses of 80 mg or 160 mg monthly, or intramuscular (i.m.) leuprolide doses of 7.5 mg monthly. Therapy was maintained for the 12‐month study. Both the intent‐to‐treat (ITT) and per protocol populations were analysed. RESULTS The primary endpoint of the trial was suppression of testosterone to ≤0.5 ng/mL at all monthly measurements from day 28 to day 364, thus defining the treatment response. This was achieved by 97.2%, 98.3% and 96.4% of patients in the degarelix 240/80 mg, degarelix 240/160 mg and leuprolide groups, respectively (ITT population). At 3 days after starting treatment, testosterone levels were ≤0.5 ng/mL in 96.1% and 95.5% of patients in the degarelix 240/80 mg and 240/160 mg groups, respectively, and in none in the leuprolide group. The median PSA levels at 14 and 28 days were significantly lower in the degarelix groups than in the leuprolide group (P