Bicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer

Prostate cancer

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

 and hirsutism

Hirsutism

Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...

. It was first launched in 1995 as a combination treatment (with surgical or medical castration) for advanced prostate cancer and subsequently launched as monotherapy for the treatment of earlier stages of the disease.

Bicalutamide is marketed by AstraZeneca

AstraZeneca

AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...

 with the brand names Casodex and Cosudex. It is recommended 50 mg once daily in combination with a luteinizing hormone-releasing hormone analogue or surgical castration.

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

Androgen receptor

The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...

 (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. Bicalutamide has been used as a molecular template for the design of selective androgen receptor modulators (SARMs) such as Andarine

Andarine

Andarine is an investigational selective androgen receptor modulator developed by GTX, Inc for treatment of conditions such as muscle wasting, osteoporosis and benign prostatic hypertrophy, using the non-steroidal androgen antagonist bicalutamide as a lead compound.Andarine is an orally active...

 and Ostarine

Ostarine

Ostarine is an investigational selective androgen receptor modulator from GTX, Inc for treatment of conditions such as muscle wasting and osteoporosis, formerly under development by Merck & Company.-Structure:According to a recent...

.

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 patients who have shown a hypersensitivity reaction to its use.
Bicalutamide is a teratogen and must not be handled by females who are or may become pregnant. It is known to cause fetal harm.
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Adverse reactions

Adverse reaction

Adverse drug reaction

An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s include reproductive system and breast disorders, breast tenderness, gynaecomastia, hot flushes, gastrointestinal disorders, diarrhoea, nausea, hepatic changes (elevated levels of transaminase

Transaminase

In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. To be specific, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to the...

s, jaundice), asthenia and pruritus.

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

Luteinizing hormone

Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

 (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, the most notable one being gynecomastia, which is often painful.

If bicalutamide is combined with an LHRH agonist

Gonadotropin-releasing hormone agonist

A gonadotropin-releasing hormone agonist is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit its biologic response, the release of the pituitary hormones FSH and LH.GnRH agonists are pregnancy category...

 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 osteoblast

Osteoblast

Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...

s) and estrogens (which reduce bone resorption by inhibiting osteoclast

Osteoclast

An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...

s) will increase bone loss and promote osteoporosis.

External links

• Casodex, Cosudex (manufacturer's website)
• Bicalutamide (patient information)