PT  - JOURNAL ARTICLE
AU  - Marc Princivalle
AU  - Pierre Broqua
AU  - Richard White
AU  - Jessica Meyer
AU  - Gaell Mayer
AU  - Lucy Elliott
AU  - Ketil Bjarnason
AU  - Robert Haigh
AU  - Christopher Yea
TI  - Rapid Suppression of Plasma Testosterone Levels and Tumor Growth in the Dunning Rat Model Treated with Degarelix, a New Gonadotropin-Releasing Hormone Antagonist
AID  - 10.1124/jpet.106.112326
DP  - 2007 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1113--1118
VI  - 320
IP  - 3
4099  - http://jpet.aspetjournals.org/content/320/3/1113.short
4100  - http://jpet.aspetjournals.org/content/320/3/1113.full
SO  - J Pharmacol Exp Ther2007 Mar 01; 320
AB  - Degarelix (FE 200486) is a member of a new class of water-soluble (>50 mg/ml) gonadotropin-releasing hormone (GnRH) antagonists in clinical development for prostate cancer. Upon subcutaneous administration, degarelix forms a gel that results in a sustained release of the compound into the circulation, immediately blocking GnRH receptors in the pituitary and inducing a fast and sustained suppression of gonadotrophin secretion in rats and primates. One of the few animal models of prostate adenocarcinoma is the Dunning R-3327H rat carcinoma transplanted into Copenhagen rats. The growth of the Dunning tumor can be inhibited by various treatments reported to be effective in the clinic, such as GnRH superagonists, antiandrogens, 5-alphareductase inhibitors, tyrosine kinase inhibitors, and surgical castration. We report in this study that degarelix produces a fast and sustained suppression of the pituitary gonadal axis in rats and a similar inhibition of tumor growth compared with surgical castration in the Dunning R-3327H rat carcinoma model. First, degarelix as been compared with d-Trp6-luteinizing hormone-releasing hormone and surgical castration on a short-term study (2 months); and second, degarelix has been compared with leuprolide and surgical castration on a long-term study (12 months). In both studies, degarelix demonstrated a sustained inhibition of tumor growth at least comparable with surgical castration. These data provide a convincing profile of degarelix as a potential candidate for the clinical management of sex steroid-dependent pathologies, such as prostate cancer, where long-term reversible chemical castration is required. The American Society for Pharmacology and Experimental Therapeutics