Although bicalutamide monotherapy increases gonadotropin and sex hormone levels in men, this will not occur if bicalutamide is combined with an antigonadotropin such as a GnRH analogue, estrogen, or progestogen, as these medications maintain negative feedback on the HPG axis.NSAA monotherapy, including with bicalutamide, shows a number of tolerability differences from methods of androgen deprivation therapy that incorporate surgical or medical castration. For example, the rates of hot flashes, depression, fatigue, and sexual dysfunction are all much higher with GnRH analogues than with NSAA monotherapy. It is thought that this is because GnRH analogues suppress estrogen production in addition to androgen production, resulting in estrogen deficiency. In contrast, NSAA monotherapy does not decrease estrogen levels and in fact increases them, resulting in an excess of estrogens that compensates for androgen deficiency and allows for a preservation of mood, energy, and sexual function. Neurosteroids that are produced from testosterone like 3α-androstanediol and 3β-androstanediol, which are ERβ agonists and the former a potent GABAA receptor positive allosteric modulator, may also be involved. In the specific case of sexual dysfunction, an additional possibility for the difference is that without concomitant suppression of androgen production, blockade of the AR by the bicalutamide in the brain is incomplete and insufficient to markedly influence sexual function.Under normal circumstances, bicalutamide has no capacity to activate the AR. However, in prostate cancer, mutations and overexpression of the AR can accumulate in prostate gland cells which can convert bicalutamide from an antagonist of the AR into an agonist.
The unique 80 mg dosage of bicalutamide used in Japan was selected for development in this country on the basis of observed pharmacokinetic differences with bicalutamide in Japanese men.Subsequent to negative findings of bicalutamide monotherapy for LPC in the EPC clinical programme, approval of bicalutamide for use specifically in the treatment of LPC was withdrawn in a number of countries including the U.K. (in October or November 2003) and several other European countries and Canada (in August 2003). In addition, the U.S. and Canada explicitly recommended against the use of 150 mg/day bicalutamide for this indication. The drug is effective for, remains approved for, and continues to be used in the treatment of LAPC and mPC, on the other hand.The patent protection of bicalutamide expired in the U.S. in March 2009 and the drug has subsequently been available as a generic, at greatly reduced cost.Bicalutamide was the fourth antiandrogen (and the third NSAA) to be introduced for the treatment of prostate cancer, following the SAA CPA in 1973 and the NSAAs flutamide in 1983 (1989 in the U.S.) and nilutamide in 1989 (1996 in the U.S.). It has been followed by abiraterone acetate in 2011, enzalutamide in 2012, apalutamide in 2018, and darolutamide in 2019, and may also be followed by in-development drugs such as proxalutamide and seviteronel. Society and culture
Generic names
Bicalutamide is the generic name of the drug in English and French and its INN, USAN, USP, BAN, DCF, AAN, and JAN.