Nonsteroidal antiandrogens (NSAA) used in prostate cancer, primarily in combination with androgen deprivation therapy (ADT) to block androgen receptor activation.
Pharmacology
| Drug | Mechanism of Action | Indications | Typical Adult Dose | Metabolism | Key Toxicities |
|---|---|---|---|---|---|
| Bicalutamide | Competitively inhibits binding of androgens (testosterone, DHT) to androgen receptors. | Metastatic prostate cancer (with LHRH agonist/antagonist); sometimes used for flare prevention at ADT initiation. | 50 mg PO once daily | Hepatic (CYP3A4) | Gynecomastia, breast tenderness, hot flashes, hepatotoxicity |
| Flutamide | Same as above | Metastatic prostate cancer (with LHRH agonist); less common now due to toxicity profile. | 250 mg PO TID | Hepatic (CYP1A2) | Diarrhea, hepatotoxicity (rare but severe), hot flashes |
| Nilutamide | Same as above | Metastatic prostate cancer (post-orchiectomy or with LHRH therapy) | 300 mg/day PO in 2–3 doses × 30 days, then 150 mg/day | Hepatic | Visual adaptation disturbance (delayed dark adaptation), interstitial pneumonitis, hepatotoxicity |
Administration & Monitoring
- With ADT: Start with LHRH agonists (leuprolide, goserelin) or antagonists (degarelix, relugolix) for optimal androgen suppression.
- Liver function tests: Baseline and periodically; monitor closely with flutamide and nilutamide.
- Counseling points:
- Nilutamide: Advise about possible visual changes and avoid driving at night until adapted.
- Bicalutamide: Taken once daily, with or without food.
- Flutamide: More frequent dosing; GI upset common.
Comparative Notes
| Feature | Bicalutamide | Flutamide | Nilutamide |
|---|---|---|---|
| Dosing frequency | Once daily | TID | Once daily (after initial higher dosing) |
| Common use | Most widely used NSAA | Rarely used now | Limited use |
| Distinct toxicity | Breast effects | GI toxicity | Visual adaptation issues, pulmonary toxicity |
Practice Pearls
- Bicalutamide is generally preferred for tolerability and convenience.
- Flutamide largely replaced due to hepatotoxicity and GI side effects.
- Nilutamide use is niche; monitor for pulmonary symptoms and vision changes.
- Always use in combination with ADT—monotherapy is not recommended for metastatic disease.
- Discontinue NSAA if progression occurs despite castrate testosterone levels (i.e., mCRPC phase).