What are alternative medications to bicalutamide (Casodex) that do not significantly increase cholesterol levels in patients with prostate cancer?

Alternative Medications to Bicalutamide That Do Not Increase Cholesterol

Enzalutamide is the preferred alternative to bicalutamide for prostate cancer treatment as it does not significantly increase cholesterol levels while offering superior progression-free survival.

Comparison of Enzalutamide vs. Bicalutamide

Efficacy

• Enzalutamide demonstrates significantly better progression-free survival compared to bicalutamide in castration-resistant prostate cancer (CRPC) patients 1
• The TERRAIN study showed median time to progression of 15.7 months with enzalutamide versus 5.8 months with bicalutamide (HR 0.44) 1
• The STRIVE trial demonstrated that enzalutamide reduced the risk of progression or death by 76% compared to bicalutamide (HR 0.24) 1
• Enzalutamide represents a category 1, preferred treatment option for patients with metastatic CRPC without prior novel hormone therapy 1

Cardiovascular and Metabolic Profile

• Unlike bicalutamide, enzalutamide has not been associated with significant hypercholesterolemia 2
• The incidence of cardiac disorders did not differ between enzalutamide and placebo arms in clinical trials 1
• Major adverse cardiovascular events occurred in only 5% of patients on enzalutamide versus 3% on placebo in the PROSPER trial 1

Side Effect Considerations

• Common side effects of enzalutamide include fatigue (33-34%), diarrhea (21%), hot flushes (20%), hypertension (12%), and headache (12%) 1
• Seizure risk with enzalutamide is low (0.6-0.9%) but should be considered in patients with seizure history 1
• Mental impairment disorders were reported in 5% of enzalutamide patients versus 2% on placebo 1

Other Alternative Options

Apalutamide

• FDA-approved for non-metastatic CRPC with PSADT ≤10 months 1
• Has not been associated with significant cholesterol elevation in clinical trials 1
• Demonstrated significant improvement in metastasis-free survival compared to placebo (40.5 vs 16.2 months) 1

Flutamide

• While flutamide is another antiandrogen option, it is less effective than enzalutamide in patients who have failed bicalutamide therapy 3
• The OCUU-CRPC study showed superior PSA response rates with enzalutamide compared to flutamide (80.8% vs 35.3% at 3 months) 3
• Flutamide causes a higher incidence of diarrhea compared to bicalutamide 4, 5

Clinical Decision Algorithm

1. First choice: Enzalutamide (160 mg daily)

   • Superior efficacy to bicalutamide 1
   • No significant impact on cholesterol levels 2
   • Category 1, preferred option per NCCN guidelines 1

2. Second choice: Apalutamide (240 mg daily)

   • For non-metastatic CRPC with PSADT ≤10 months 1
   • No significant cholesterol elevation reported 1

3. Consider patient-specific factors:

   • For patients concerned about sexual function: Note that bicalutamide better preserves sexual interest and physical capacity compared to castration 6, 7, 8
   • For patients with seizure history: Use caution with enzalutamide (0.6-0.9% seizure risk) 1
   • For patients with cognitive concerns: Be aware of mental impairment risk with enzalutamide (5%) 1

Important Considerations and Monitoring

• Patients receiving enzalutamide have no food restrictions, and concurrent prednisone is permitted but not required 1
• Regular monitoring for side effects including fatigue, hypertension, and mental status changes is recommended 1
• All patients should continue LHRH agonist/antagonist therapy when switching from bicalutamide to enzalutamide 1
• Cost considerations may influence treatment selection, as enzalutamide is more expensive than bicalutamide 1, 6