The development of Casodex (bicalutamide): preclinical studies

Eur Urol. 1996;29 Suppl 2:83-95. doi: 10.1159/000473846.


Casodex (bicalutamide, Zeneca Limited) was developed for the treatment of prostate cancer from a series of nonsteroidal compounds related to flutamide. Casodex is a selective antiandrogen that binds to rat, dog and human prostate androgen receptors, and has approximately a 4-fold higher affinity for the rat androgen receptor than hydroxyflutamide, the active metabolite of flutamide. Casodex also binds to androgen receptors found in the LNCaP human prostate tumour and the Shionogi S115 mouse mammary tumour cell line, as well as androgen receptors transfected into CV-1 and HeLa cells. In all cases, Casodex behaves as a 'pure' antiandrogen and inhibits gene expression and cell growth stimulated by androgens. Studies in vivo show that Casodex is a potent antiandrogen in the rat. In contrast to flutamide, which produces dose-related, marked increases in serum luteinising hormone (LH) and testosterone, Casodex has little effect on serum LH and testosterone; that is, it is peripherally selective. The peripheral selectivity of Casodex has now been shown to be due to poor penetration across the blood-brain barrier. In dogs, Casodex has exquisite potency and causes dose-related atrophy of the prostate gland and epididymis; with an oral ED50 of 0.1 mg/kg, it is about 50 times as potent as flutamide in this species. Casodex is also peripherally selective in the dog. In addition, magnetic resonance imaging studies have shown that Casodex is a potent antiandrogen in the monkey. Casodex, at a daily oral dose of 25 mg/kg effected a highly significant reduction in the growth of Dunning R3327H transplantable rat prostate tumours that was equivalent to that achieved by either surgical or medical castration with the LH-releasing hormone agonist Zoladex (goserelin). In a comparative study, flutamide was shown to be both less potent and less active than Casodex. In these preclinical studies, Casodex was well tolerated. The preclinical properties of Casodex give it advantages, with respect to potency, tolerability and the maintenance of effective antiandrogen serum concentrations, over other available antiandrogens. Moreover, it has a half-life that is compatible with once-daily administration.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / metabolism
  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use*
  • Anilides / metabolism
  • Anilides / pharmacology
  • Anilides / therapeutic use*
  • Anilides / toxicity
  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Binding, Competitive
  • Blood-Brain Barrier
  • Disease Models, Animal
  • Dogs
  • Drug Evaluation, Preclinical
  • Humans
  • Macaca nemestrina
  • Male
  • Nitriles
  • Orchiectomy
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / surgery
  • Rats
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / metabolism
  • Tosyl Compounds
  • Tumor Cells, Cultured


  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents
  • Nitriles
  • Receptors, Androgen
  • Tosyl Compounds
  • bicalutamide