"Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies.
The relative merits of the steroidal anti-androgen, cyproterone acetate, and the non-steroidal anti-androgens flutamide and nilutamide, are reviewed. It is concluded that pure anti-androgens offer some advantages over cyproterone acetate but that they each have some features which merit improvement. A new compound which was a pure anti-androgen, peripherally selective, well tolerated with a long half-life would have significant advantages. Preclinical studies in rats and dogs show that Casodex (ICI 176,334) is a potent pure anti-androgen which is well tolerated and has a long half-life. Casodex induces marked regression of the prostate yet fails to cause the substantial elevation in serum LH and testosterone seen with flutamide and nilutamide; it is thus peripherally selective. Casodex is as effective as surgical or medical castration with Zoladex in limiting the growth of the transplantable androgen-responsive Dunning rat prostate tumour. Such a profile makes Casodex a strong candidate as the future anti-androgen of choice for the treatment of prostate cancer and benign prostate hypertrophy.
Furr
B J
BJ
Bioscience I, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
D000726:Androgen Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000813:Anilides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003534:Cyproterone / Q000031:analogs & derivatives / Q000627:therapeutic use; D017373:Cyproterone Acetate; D004285:Dogs; D005485:Flutamide / Q000627:therapeutic use; D007093:Imidazoles / Q000627:therapeutic use; D048289:Imidazolidines; D008297:Male; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D007093:Imidazoles; D048289:Imidazolidines; D009570:Nitriles; D014105:Tosyl Compounds; D017373:Cyproterone Acetate; C021277:nilutamide; D005485:Flutamide; C053541:bicalutamide; D003534:Cyproterone