CASODEX

Indications

• Locally advanced prostate cancer
• Metastatic prostate cancer
• Hormone-responsive malignancies

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Adult: 150 mg once daily.

Mechanism of action

Bicalutamide competes with androgens for binding to androgen receptors, effectively blocking their action. This inhibition affects normal and malignant prostatic tissue growth by preventing androgen-dependent DNA and protein synthesis. Its action results in tumor growth arrest or regression, making it a crucial therapy in managing hormone-responsive malignancies such as prostate cancer.

Pharmacodynamics

As a selective antiandrogen, Bicalutamide does not exhibit androgenic, progestational, or glucocorticoid activity. It has a high binding affinity for androgen receptors, exceeding that of similar agents. The drug disrupts feedback mechanisms in the hypothalamus, leading to increased luteinizing hormone release and transiently elevated testosterone levels, which can initially appear counterproductive but ultimately supports its therapeutic role.

Pharmacokinetics

Bicalutamide is administered orally and exhibits extensive protein binding. Its metabolism occurs in the liver, primarily through cytochrome P450 enzymes, and it has a half-life that allows for once-daily dosing. The pharmacokinetics can be influenced by hepatic function, requiring caution in patients with liver impairment. The drug is also excreted in urine and feces, with considerations for dosing adjustments in renal impairment.

Contra-indications

• History or risk of seizures
• History or risk of QT-interval prolongation
• Severe hepatic impairment

Adverse effects

• Fatigue
• Decreased appetite
• Hot flushes
• Breast tenderness
• Chest pain
• Gynecomastia
• Nausea
• Oedema
• Sexual dysfunction
• QT interval prolongation
• Seizures (rare)
• Photosensitivity reaction (rare)

Interactions

• Bicalutamide may increase exposure to lomitapide
• Caution is advised with other medications that can prolong the QT interval

Precautions

• Monitor liver function periodically during treatment
• Caution in patients with moderate to severe hepatic impairment
• Caution in patients with renal impairment
• Risk of photosensitivity

Pregnancy

Bicalutamide is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known whether bicalutamide is excreted in human milk; caution is advised.

Storage

Store at room temperature in a dry place, away from light.

Formulations

• Tablets: 50 mg, 150 mg

Mechanism of action

Bicalutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin which stimulate the growth of normal and malignant prostatic tissue. Bicalutamide is a nonsteroidal antiandrogen that is structurally and pharmacologically related to flutamide and nilutamide. Bicalutamide inhibits the action of androgens by competitively blocking nuclear androgen receptors in target tissues such as the prostate, seminal vesicles, and adrenal cortex; blockade of androgen receptors in the hormone-sensitive tumor cells may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis. Bicalutamide is a selective antiandrogen with no androgenic or progestational activity in various animal models. The relative binding affinity of bicalutamide at the androgen receptor is more than that of nilutamide and approximately 4 times that of hydroxyflutamide, the active metabolite of flutamide. Common pharmacologic therapies for prostate cancer (ie, gonadotropin-releasing hormone [GnRH] analogs, nonsteroidal antiandrogens) when used as monotherapy initially result in increased serum testosterone concentrations, which may limit the effects of the drugs. Androgen receptors in the hypothalamus are blocked by bicalutamide, which disrupts the inhibitory feedback of testosterone on luteinizing hormone (LH) release, resulting in a temporary increase in secretion of LH; the increase in LH stimulates an increase in the production of testosterone. As GnRH analogs have potent GnRH agonist properties, testicular steroidogenesis continues during the first few weeks after initiating therapy. However, the combination of orchiectomy or GnRH analog therapy to suppress testicular androgen production and an antiandrogen to block response of remaining adrenal androgens provides maximal androgen blockade. Concomitant administration of antiandrogens such as bicalutamide in patients initiating therapy with a GnRH analog can inhibit initial androgenic stimulation and potential exacerbation of symptoms (e.g., bone pain, urinary obstruction, liver pain, impending spinal cord compression) that may occur during the first month of GnRH analog therapy. Bicalutamide was developed from a series of nonsteroidal compounds related to flutamide that showed a range of pharmacologic activity from full androgen agonist to pure antiandrogen, including progestational and antiprogestational properties. Bicalutamide is a pure antiandrogen that binds to rat, dog, and human prostate; the affinity compared with the natural ligand 5 alpha-dihydrotestosterone is low, but bicalutamide has an affinity for the rat androgen receptor approximately four times higher than hydroxyflutamide, the active metabolite of flutamide. Bicalutamide also binds to androgen receptors found in the LNCaP human prostate tumor and the Shionogi S115 mouse mammary tumor cell line, as well as androgen receptors transfected into CV-1 and HeLa cells. In all cases, bicalutamide behaves as a pure antiandrogen and inhibits gene expression and cell growth stimulated by androgen. Studies with the LNCaP cell line are particularly interesting, as these cells contain a mutated androgen receptor (codon 868, Thr-->Ala), which behaves idiosyncratically with other antiandrogens (cyproterone acetate and flutamide): both these antiandrogens act as agonists in this cell line and stimulate proliferation. Studies in vivo show that bicalutamide is a potent antiandrogen in the rat. In immature, castrated male rats treated daily with testosterone propionate, bicalutamide produces a profound inhibition of accessory sex organ (ventral prostate and seminal vesicles) growth at oral doses as low as 0.25 mg/kg; it is more active in this test than flutamide or cyproterone acetate. In mature male rats, daily oral doses of bicalutamide produce a dose-related reduction in weights of the ventral prostate glands and semina

Pharmacodynamics

Bicalutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Bicalutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Bicalutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration.