What is the best treatment approach for an elderly male patient with a history of prostate cancer, who has undergone bilateral orchiectomy and developed castrate-resistant prostate cancer, considering Abiraterone (abiraterone acetate) therapy?

Abiraterone for Castrate-Resistant Prostate Cancer

For an elderly male patient with castrate-resistant prostate cancer (CRPC) after bilateral orchiectomy, abiraterone acetate 1,000 mg once daily plus prednisone 5 mg twice daily is a Category 1 recommended treatment that significantly improves overall survival and should be initiated. 1

Dosing and Administration

• Standard dosing: Abiraterone acetate 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily on an empty stomach (at least 1 hour before or 2 hours after meals) plus prednisone 5 mg twice daily 2
• Alternative dosing: 250 mg once daily with a low-fat breakfast may be considered to reduce financial toxicity and improve compliance, though this is a Category 2B recommendation 1
• Continue ADT: Although this patient has undergone bilateral orchiectomy (surgical castration), the principle of maintaining castrate testosterone levels (<50 ng/dL) remains critical 1, 3

Evidence for Efficacy in CRPC

Post-Docetaxel Setting (Category 1)

• In the pivotal COU-AA-301 trial, abiraterone plus prednisone significantly improved overall survival compared to prednisone alone (14.8 vs 10.9 months; HR 0.65; P<0.001) in men with metastatic CRPC who had received prior docetaxel 1
• This represents the strongest evidence base and FDA approval for post-chemotherapy CRPC 1, 2

Pre-Docetaxel Setting

• Asymptomatic/minimally symptomatic patients: Abiraterone is a standard option (Category 1) based on the COU-AA-302 trial showing improved radiographic progression-free survival and overall survival 1
• Symptomatic patients not amenable to docetaxel: Abiraterone represents an appropriate therapy given its survival and palliative benefit with reasonable toxicity (Category 2B) 1

Special Considerations for Elderly Patients

Critical caveat: The STAMPEDE trial demonstrated that survival benefit of abiraterone was larger in men <70 years of age than in older men (HR 0.51 vs 0.94) 1

• Older men experienced increased toxicities with higher incidences of grade 3-5 adverse events (47% vs 33%) and treatment-related deaths (9 vs 3) 1
• However, a dedicated analysis of elderly patients (≥75 years) in COU-AA-302 showed that abiraterone still demonstrated clinical benefit and was well tolerated, supporting its use as a treatment option for elderly patients who may not tolerate other therapies 4

Mandatory Monitoring Requirements

Baseline Assessment

• Blood pressure, serum potassium, liver function tests (ALT, AST, bilirubin), and cardiac evaluation 1, 2

Ongoing Monitoring

• Mineralocorticoid excess effects: Monitor blood pressure and serum potassium regularly due to risk of hypertension (10% severe), hypokalemia (28%), and fluid retention/edema 1, 5
• Hepatotoxicity: Grade 3-5 liver toxicity occurs in 7% of patients; monitor liver function tests 1, 2
• Cardiac disorders: Severe cardiac events noted in 10% of men, including atrial fibrillation and cardiac failure 1
• PSA and imaging: PSA every 3-6 months and conventional imaging every 6-12 months 6

Dose Modifications for Hepatotoxicity

If ALT/AST >5× ULN or total bilirubin >3× ULN: 2

• Interrupt abiraterone treatment
• May restart at 750 mg once daily after return to baseline or AST/ALT ≤2.5× ULN and bilirubin ≤1.5× ULN
• If hepatotoxicity recurs at 750 mg, may restart at 500 mg once daily
• Permanently discontinue if concurrent ALT >3× ULN and total bilirubin >2× ULN occurs

Common Pitfalls to Avoid

• Food interaction: Abiraterone must be taken on an empty stomach as food significantly increases drug exposure and toxicity risk 2
• Inadequate corticosteroid coverage: Prednisone 5 mg twice daily is mandatory to prevent ACTH-mediated mineralocorticoid excess 1, 2
• Dose escalation at progression: Increasing abiraterone to 2,000 mg daily at disease progression has no clinical benefit and cannot be recommended 7
• Inadequate monitoring in elderly: Given the increased toxicity profile in older men, more vigilant monitoring of blood pressure, cardiac function, and hepatic function is essential 1

Expected Adverse Events

• Most common (>5%): Joint swelling/discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia 1
• Serious events requiring discontinuation: Elevated transaminases, urosepsis, or cardiac failure (each <1%) 1
• Overall discontinuation rate due to adverse events is approximately 12% 1