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Bicalutamide: Hormonal Treatment of Advanced Prostate Cancer

Indications for Bicalutamide

Anti-androgen hormone treatment of prostate cancer with bicalutamide is a therapeutic option against prostate cancer in the following situations:

• Hormonal treatment of advanced prostate cancer, either alone or in combination with a GnRH agonist, GnRH antagonist or surgical castration.
• Adjuvant androgen deprivation therapy of advanced prostate cancer after surgery or radiation therapy.
• Short course of 14 days to prevent the testosterone flare at the beginning of GnRH agonist therapy.

Mechanism of Action of Bicalutamide

Bicalutamide is a nonsteroidal anti-androgen drug, which shows competitive antagonism in relation to the androgen receptor. The central inhibition of androgen receptors leads to an increase in LH, testosterone and estrogen.

Pharmacokinetics of Bicalutamide

• Good absorption after oral ingestion
• Over 95% plasma protein binding
• Hepatic metabolism, renal and biliary excretion. Elimination half life: 1.3 days. Metabolites from bicalutamide are pharmacologically active and lead to an effective half life of 7 days for active metabolites.

Side Effects of Bicalutamide

• Bicalutamide shows typical side effects of antiandrogens: gynecomastia, hot flushes, decreased libido, decreased erectile function. Sexual side effects are less pronounced than with LHRH treatment.
• Abdominal pain, diarrhea or nausea (15%), rarely vomiting.
• Increased liver enzymes (7%) or jaundice.
• Fluid retention, cardiac decompensation
• Anemia (frequently), rarely leukopenia, thrombocytopenia
• Allergic reactions

Interactions with Bicalutamide

Increased effect of warfarin (displacement from the plasma protein binding), terfenadine or cisapride (inhibition of cytochromes).

Contraindications for Bicalutamide

Increased liver enzymes warrant dose reduction and regular laboratory monitoring. Bicalutamide should be stopped in progressive elevation of liver transaminases without evidence of liver metastases. Further contraindications are allergy, bicalutamide has no indications in women and children.

Dosage of Bicalutamide

In the EU and some other countries, two dosages of bicalutamide for oral administration are approved: 50 mg/day or 150 mg/day. In the USA, the usage of bicalutamide is only approved for the 50 mg indication:

150 mg/day bicalutamide is recommended for antiandrogenic monotherapy (as an alternative to treatment with GnRH modulators or surgical castration).

50 mg/day bicalutamide is sufficient to prevent the testosterone flare at the beginning of GnRH agonist therapy or in combination with GnRH agonist treatment (maximal androgen blockade, MAB).

References

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