Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer.
BACKGROUND
Degarelix is a gonadotropin-releasing hormone antagonist (GnRH receptor blocker) with immediate onset of action, suppressing gonadotropins, testosterone, and prostate-specific antigen (PSA) in prostate cancer.


OBJECTIVE
To determine the efficacy and safety of initial doses of 200 mg or 240 mg of degarelix and thereafter monthly subcutaneous maintenance doses of 80 mg, 120 mg, or 160 mg of degarelix for the treatment of prostate cancer.


METHODS
The 1-yr study was of open-label, randomised design and involved 187 patients (range: 52-93 yr, median: 72 yr) with histologically confirmed adenocarcinoma of the prostate and a baseline PSA >2 ng/ml.


CONCLUSIONS
At baseline, median serum testosterone was 4.13 ng/ml (range: P25-P75, 3.37-5.19 ng/ml) and PSA was 27.6 ng/ml (range: P25-P75, 11.9-55.0 ng/ml). On day 3, 88% and 92% of patients in the groups to whom 200-mg and 240-mg initial doses of degarelix were administered, respectively, had testosterone levels < or =0.5 ng/ml. For patients with testosterone levels < or =0.5 ng/ml at 1 mo, the testosterone levels remained < or =0.5 ng/ml until the end of the study in 100% of the patients treated with a monthly maintenance dosage of 160 mg of degarelix. No evidence of testosterone surge was detected. PSA decreased by 97-98% after 1 yr and the median time to 90% reduction in PSA was 8 wk in all but one patient (from the 80-mg dosage treatment group at the initial 200-mg dose of degarelix). Thirteen patients (6%) withdrew from the study due to adverse events, largely related to androgen deprivation.


CONCLUSIONS
Degarelix treatment for 1 yr resulted in a fast, profound, and sustained suppression of testosterone and PSA, with no evidence of testosterone surge. Degarelix was well tolerated.
Van Poppel
Hendrik
H
Department of Urology, UZ Gasthuisberg, Leuven, Belgium. hendrik.vanpoppel@uzleuven.be
Tombal
Bertrand
B
de la Rosette
Jean J
JJ
Persson
Bo-Eric
BE
Jensen
Jens-Kristian
JK
Kold Olesen
Tine
T
D000368:Aged; D000369:Aged, 80 and over; D000090266:Chromobox Protein Homolog 5; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013997:Time Factors
C000715594:CBX5 protein, human; D009842:Oligopeptides; D011966:Receptors, LHRH; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D000090266:Chromobox Protein Homolog 5