Bicalutamide 90357-06-5

Description and mechanism of action

Bicalutamide is an oral non-steroidal anti-androgen with the empirical formula C₁₈H₁₄F₄N₂O₄S and is an off-white powder that is practically insoluble in water. Bicalutamide acts as a pure anti-androgen by binding to the androgen receptor (AR) and preventing the activation of the AR and subsequent upregulation of androgen responsive genes by androgenic hormones. In addition, bicalutamide accelerates the degradation of the androgen receptor.

Indications and use

Bicalutamide is indicated for the treatment of stage D2 metastatic prostate cancer in combination with a luteinizing hormone-releasing hormone analogue or as a monotherapy. It has also been used in clinical trials for ovarian cancer. It has also been used in combination with castration. Most advanced prostate cancer patients eventually become resistant to antiandrogen including bicalutamide therapy.

Contraindications and precautions

Bicalutamide is contraindicated in females and children and must not be given to any patient who has shown a hypersensitivity reaction to its use.

Physiology

Bicalutamide blocks androgen receptors. This prevents testosterone and other androgens from binding to the receptors. Bicalutamide may cause sexual difficulties and a decline in sperm count. Nevertheless bicalutamide monotherapy appears to have minimal effect on sexual activity. Blockade of androgens receptors by bicalutamide in the brain will eliminate the negative feedback loop of testosterone on the release of luteinizing hormone (LH). This in turn will lead to a dramatic increase in testosterone and estrogen levels. Bicalutamide treatment will block the effects of rising testosterone levels but the effect of rising estrogen levels will remain unopposed and lead to feminizing effects most notably gynecomastia which is often painful. If bicalutamide is combined with an LHRH agonist or surgical castration then the elevation of estrogen levels will be prevented and the risks of excessive estrogen will be reduced. However since both testosterone and estrogens are essential for normal bone metabolism, reducing the anabolic bone effects of both androgens (which increase bone formation by stimulating osteoblasts) and estrogens (which reduce bone resorption by inhibiting osteoclasts) will increase bone loss and promote osteoporosis.