What is the recommended treatment for metastatic castration-resistant prostate cancer (mCRPC) using abiraterone (Zytiga) and prednisone?

Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Abiraterone and Prednisone

Abiraterone acetate 1,000 mg daily combined with prednisone 5 mg twice daily is the standard treatment for metastatic castration-resistant prostate cancer (mCRPC), with strong evidence showing improved overall survival and radiographic progression-free survival. 1

Dosing and Administration

• Abiraterone acetate should be administered at a dose of 1,000 mg (four 250-mg tablets) orally once daily on an empty stomach, at least 1 hour before or 2 hours after a meal 1
• Prednisone must be administered at 5 mg orally twice daily concurrently with abiraterone to prevent mineralocorticoid excess side effects 2, 1
• Patients should continue receiving a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy to maintain castrate levels of testosterone 1
• The fine-particle formulation of abiraterone (500 mg daily) with methylprednisolone (4 mg twice daily) is an alternative option with bioequivalent efficacy 2
• A lower-cost alternative dosing of abiraterone 250 mg/day taken with a low-fat breakfast has shown non-inferiority to the standard 1,000 mg fasting dose in a phase II trial 2

Efficacy Evidence

• In the COU-AA-302 trial of chemotherapy-naïve mCRPC patients, abiraterone plus prednisone significantly improved:
  • Overall survival (median 35.3 vs 30.1 months; HR: 0.79) 2, 3
  • Radiographic progression-free survival (median 16.5 vs 8.2 months; HR: 0.52) 2, 3
  • Time to pain progression, next subsequent therapy, initiation of chemotherapy, and PSA progression 3
• Abiraterone is effective in both asymptomatic/minimally symptomatic patients and those with symptomatic disease 2
• The drug is FDA-approved for mCRPC patients regardless of whether they have received prior docetaxel chemotherapy 1

Monitoring and Side Effect Management

• Regular monitoring is essential for:

  • Liver function tests (monthly, at least initially) 2, 1
  • Serum potassium and phosphate levels (monthly, at least initially) 2, 1
  • Blood pressure readings (monthly, at least initially) 2, 1
  • Symptom-directed cardiac assessment, particularly in patients with pre-existing cardiovascular disease 2

• Common adverse events (>5%) include:

  • Fatigue (39%), joint/back discomfort (28-32%), peripheral edema (28%) 2
  • Hypertension (22%, severe in 4%), hypokalemia (17%), hypophosphatemia (24%) 2
  • Hot flushes (22%), diarrhea/nausea/constipation (22%) 2
  • Atrial fibrillation (4%), muscle discomfort (14%) 2
  • Urinary tract infection, cough, urinary frequency, nocturia, dyspepsia 2

• Serious adverse events that may require dose modification or discontinuation:

  • Elevated liver enzymes (AST/ALT) 2, 1
  • Cardiac disorders 2, 1
  • Severe hypertension or hypokalemia 2, 1

Special Considerations

• For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the starting dose to 250 mg once daily 1
• If hepatotoxicity develops during treatment, hold abiraterone until recovery; retreatment may be initiated at a reduced dose 1
• Discontinue abiraterone if severe hepatotoxicity develops 1
• Avoid concomitant strong CYP3A4 inducers; if necessary, increase abiraterone dosing frequency 1
• Use caution when co-administering with CYP2D6 substrates that have a narrow therapeutic index 1
• Spironolactone should be avoided as it can interfere with abiraterone's mechanism of action 4

Alternative Treatment Options

• For patients who cannot tolerate abiraterone plus prednisone, enzalutamide is a preferred alternative 4
• Docetaxel-based chemotherapy is appropriate for patients with symptomatic disease or visceral metastases 4
• Radium-223 is specifically indicated for patients with symptomatic bone metastases without known visceral disease 4

Treatment Resistance Management

• Switching from prednisone to dexamethasone 1 mg/day can be considered for patients with disease progression on abiraterone 2
• Increasing the dose of abiraterone at the time of resistance (to 1000 mg twice daily) has limited clinical utility and is not recommended 5

By following these evidence-based recommendations for abiraterone plus prednisone in mCRPC, clinicians can optimize treatment outcomes while effectively managing potential adverse events.