What is the recommended treatment regimen for metastatic castration-resistant prostate cancer using Abiraterone (abiraterone acetate)?

Abiraterone Treatment Regimen for Metastatic Castration-Resistant Prostate Cancer

For metastatic castration-resistant prostate cancer (mCRPC), administer abiraterone acetate 1,000 mg orally once daily on an empty stomach (at least 1 hour before or 2 hours after meals) combined with prednisone 5 mg orally twice daily, while continuing androgen deprivation therapy indefinitely. 1, 2

Standard Dosing Protocol

• Abiraterone acetate: 1,000 mg (four 250 mg tablets or two 500 mg tablets) taken once daily 1
• Prednisone: 5 mg orally twice daily (required to prevent mineralocorticoid excess side effects including hypertension, hypokalemia, and edema) 2, 1
• Timing: Must be taken on an empty stomach with water only—at least 1 hour before or 2 hours after any food 1
• Tablets: Swallow whole; do not crush or chew 1
• Concurrent therapy: Continue GnRH analog or maintain bilateral orchiectomy status 1

Alternative Dosing Options

Fine-particle formulation: 500 mg daily with methylprednisolone 4 mg twice daily is bioequivalent and represents a Category 2B alternative 3, 2

Lower-cost regimen: 250 mg daily taken with a low-fat breakfast showed non-inferiority to standard 1,000 mg fasting dose in phase II trials, though this remains investigational 2

Clinical Efficacy Evidence

The recommendation is based on robust survival data from pivotal trials:

• COU-AA-302 trial (chemotherapy-naïve mCRPC): Median overall survival improved from 30.1 to 35.3 months (HR 0.79), with radiographic progression-free survival extending from 8.2 to 16.5 months (HR 0.52) 2, 4
• Post-docetaxel setting: Median overall survival was 14.8 months versus 10.9 months with placebo (HR 0.65) 5
• Abiraterone demonstrates efficacy in both asymptomatic/minimally symptomatic patients and those with symptomatic disease 2

Required Monitoring

Monthly assessments are essential and must include 2, 6:

• Blood pressure measurements
• Serum potassium levels
• Serum phosphate levels
• Liver function tests (ALT, AST, bilirubin)

Baseline and ongoing monitoring should track for mineralocorticoid excess manifestations and hepatotoxicity 2, 6

Common Adverse Events

Expect the following side effects (>5% incidence) 2:

• Fatigue
• Joint and back discomfort
• Peripheral edema
• Hypertension
• Hypokalemia
• Hypophosphatemia
• Hot flushes
• Hepatotoxicity

These adverse events are generally mild and manageable with standard medical interventions, though they occur more frequently than with placebo 3, 5

Dose Modifications for Hepatic Impairment

Moderate hepatic impairment (Child-Pugh Class B): Reduce starting dose to 250 mg once daily with enhanced monitoring (weekly liver function tests for first month, every 2 weeks for next 2 months, then monthly) 1

Severe hepatic impairment (Child-Pugh Class C): Do not use abiraterone 1

Management of Hepatotoxicity During Treatment

If ALT/AST >5× ULN or total bilirubin >3× ULN develops 1:

1. Interrupt treatment immediately
2. Restart at 750 mg daily once liver function returns to baseline or AST/ALT ≤2.5× ULN and bilirubin ≤1.5× ULN
3. Monitor every 2 weeks for 3 months, then monthly
4. If hepatotoxicity recurs at 750 mg: Reduce to 500 mg daily after recovery
5. If hepatotoxicity recurs at 500 mg: Discontinue permanently

Critical Drug Interaction

Avoid spironolactone: This mineralocorticoid receptor antagonist interferes with abiraterone's mechanism of action and should not be used concurrently 7

Disease Progression Management

Switch corticosteroid: Consider changing from prednisone to dexamethasone 1 mg daily for patients experiencing disease progression on abiraterone 2

Special Population: Diabetes

Severe hypoglycemia risk: Patients taking thiazolidinediones (including pioglitazone) or repaglinide require close blood glucose monitoring and potential antidiabetic medication dose adjustments 1

Treatment Duration

Continue abiraterone until disease progression, unacceptable toxicity, or initiation of subsequent mCRPC treatments 3

Quality of Life Benefits

Beyond survival advantages, abiraterone treatment improves 3:

• Pain intensity progression
• Fatigue levels
• Functional status
• Prostate cancer-related symptoms
• Overall health-related quality of life