What is bicalutamide?

What is Bicalutamide?

Bicalutamide is a nonsteroidal androgen receptor inhibitor (antiandrogen) used primarily in the treatment of prostate cancer, either as monotherapy at 150 mg daily for early-stage disease or at 50 mg daily in combination with LHRH agonists for advanced metastatic prostate cancer. 1

Mechanism of Action

• Bicalutamide competitively inhibits androgen action by binding to cytosol androgen receptors in target tissues, blocking the effects of testosterone on prostate cancer cells 1
• The drug is a racemate, with antiandrogenic activity residing almost exclusively in the R-enantiomer; the S-enantiomer is essentially inactive 1, 2
• Unlike castration therapies, bicalutamide does not suppress testosterone production—serum testosterone levels may actually rise by up to 80% but typically remain within normal range 2

Clinical Formulations and Dosing

• Standard tablet strength: 50 mg, taken once daily 1
• Approved dosing regimens:
  • 50 mg daily in combination with LHRH agonists for Stage D2 metastatic prostate cancer 1
  • 150 mg daily as monotherapy (though the 150 mg dose is not FDA-approved for use alone or with other treatments in the U.S.) 1
• The long elimination half-life (approximately 5.8 days for the active R-enantiomer) permits convenient once-daily dosing 1, 2

Pharmacokinetic Properties

• Absorption: Well-absorbed orally; food does not significantly affect absorption 1, 2
• Protein binding: Highly protein-bound at 96% 1
• Metabolism: Extensively metabolized by the liver, primarily through CYP3A4 and glucuronidation pathways 2
• Accumulation: The R-enantiomer accumulates approximately 10-fold at steady state, with steady-state concentrations around 9 mcg/mL at the 50 mg dose 1, 2
• Elimination: Metabolites are excreted equally in urine and feces, with minimal unchanged drug in urine 2

Clinical Efficacy Context

• When combined with LHRH agonists, bicalutamide 50 mg daily demonstrates equivalent or superior efficacy compared to flutamide 250 mg three times daily, with better tolerability 3
• The National Comprehensive Cancer Network notes that bicalutamide monotherapy better preserves sexual interest and physical capacity compared to castration, though this must be balanced against potential efficacy differences 4
• For castration-resistant prostate cancer, newer agents like enzalutamide demonstrate superior progression-free survival (15.7 vs 5.8 months) compared to bicalutamide 4, 5

Important Safety Considerations

• Liver toxicity: Severe liver problems, including liver failure requiring hospitalization or leading to death, have occurred; liver function tests should be performed before and during treatment 1
• Gynecomastia and breast pain: Occur in up to 90% of patients on 150 mg monotherapy; prophylactic tamoxifen 20 mg daily or breast bud radiotherapy within the first month can prevent this 6
• Contraindications: Absolutely contraindicated in women, pregnancy, and patients with known hypersensitivity to bicalutamide 1
• Drug interactions: May affect warfarin metabolism and other medications; careful monitoring is required 1

Practical Clinical Points

• Can be taken with or without food, but should be taken at the same time each day (morning or evening) 1
• Treatment should start simultaneously with LHRH agonist therapy when used in combination 1
• Males with female partners of childbearing potential should use effective contraception during treatment and for 130 days after the final dose 1
• Patients should avoid excessive sun exposure due to potential photosensitivity 1