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

Abiraterone Treatment Regimen for Castration-Resistant Prostate Cancer

For patients with metastatic castration-resistant prostate cancer (mCRPC), the recommended treatment regimen is abiraterone acetate 1,000 mg orally once daily with prednisone 5 mg orally twice daily, taken on an empty stomach. 1, 2

Dosing and Administration Details

• Standard dosing: 1,000 mg abiraterone acetate once daily with prednisone 5 mg twice daily 1, 2
• Administration timing: Must be taken on an empty stomach with water at least 1 hour before or 2 hours after a meal 2
• Alternative cost-saving dosing: 250 mg/day taken with a low-fat breakfast (non-inferior to standard dosing) 1
• Concurrent therapy: Patients should continue receiving a gonadotropin-releasing hormone (GnRH) analog or should have had bilateral orchiectomy to maintain castrate testosterone levels (<50 ng/dL) 1, 2

Alternative Formulation

• Fine-particle formulation: 500 mg daily plus methylprednisolone 4 mg twice daily (bioequivalent to standard formulation) 1
• This formulation is considered a category 2A option by NCCN 1

Monitoring Requirements

Regular monitoring is essential during abiraterone therapy:

• Blood pressure readings (monthly)
• Liver function tests (monthly)
• Potassium and phosphate levels (monthly)
• Symptom-directed assessment for cardiac disease, particularly in patients with pre-existing cardiovascular disease 1

Common Adverse Effects

The most common adverse reactions (>5%) include:

• Fatigue (39%)
• Back or joint discomfort (28-32%)
• Peripheral edema (28%)
• Gastrointestinal symptoms: diarrhea, nausea, or constipation (22%)
• Hypokalemia (17%)
• Hypophosphatemia (24%)
• Hypertension (22%, severe in 4%)
• Hot flushes (22%) 1

Management of Disease Progression

For patients experiencing disease progression on standard abiraterone therapy:

• Consider switching from prednisone to dexamethasone 1 mg/day, which has shown improved PSA responses and progression-free survival 1
• Note that increasing the dose of abiraterone to 1,000 mg twice daily at the time of resistance has limited clinical utility and is not recommended 3

Special Considerations

• Hepatic impairment: For patients with moderate hepatic impairment (Child-Pugh Class B), reduce the starting dose to 250 mg once daily 2
• Hepatotoxicity management: Hold abiraterone until recovery for patients who develop hepatotoxicity during treatment; retreatment may be initiated at a reduced dose; discontinue for severe hepatotoxicity 2
• Elderly patients: Patients ≥70 years may experience increased toxicities, including higher incidences of grade 3-5 adverse events 1

Efficacy in mCRPC

Abiraterone is a category 1, preferred option for mCRPC without prior novel hormone therapy according to NCCN guidelines 1. For patients with mCRPC and prior novel hormone therapy, abiraterone is included in the "other recommended regimens" category 1.

Common Pitfalls to Avoid

1. Failing to monitor for mineralocorticoid excess: Severe hypertension or cardiac disorders occur in 10% of patients and grade 3-5 liver toxicity in 7% 1
2. Improper administration: Taking with food significantly alters absorption; standard dosing requires an empty stomach 2
3. Discontinuing GnRH analog: ADT should be continued to maintain castrate serum levels of testosterone 1
4. Inadequate monitoring: Regular assessment of liver function, potassium, phosphate, and blood pressure is essential 1
5. Drug interactions: Avoid concomitant strong CYP3A4 inducers and use caution with CYP2D6 substrates 2

Abiraterone has demonstrated significant clinical benefit in mCRPC, with studies showing improved overall survival and radiographic progression-free survival compared to placebo 1. The treatment should be continued until disease progression or unacceptable toxicity occurs.