What prednisone dose should be given with abiraterone acetate (Zytiga) in a patient with metastatic prostate cancer and bone pain?

Prednisone Dosing with Abiraterone for Metastatic Prostate Cancer

The standard dose is prednisone 5 mg orally twice daily (total 10 mg/day) given continuously with abiraterone 1,000 mg once daily on an empty stomach until disease progression or intolerable toxicity. 1, 2

Standard Dosing Regimen

• Abiraterone acetate 1,000 mg once daily taken on an empty stomach (at least 1 hour before or 2 hours after food) 2
• Prednisone 5 mg orally twice daily (morning and evening, total 10 mg/day) 1, 2
• Continue both agents until clinical or radiographic progression or unacceptable toxicity 1, 3
• This regimen demonstrated improved overall survival (34.7 vs 30.3 months, HR 0.81, P=0.003) and significantly delayed time to pain progression in the pivotal COU-AA-302 trial 1

Critical Rationale for Prednisone

• Prednisone is mandatory, not optional, because abiraterone's CYP17A1 inhibition causes upstream accumulation of mineralocorticoid precursors (deoxycorticosterone, corticosterone), leading to hypertension (22% of patients), hypokalemia (17%), and peripheral edema (28%) 1, 4
• The 5 mg twice-daily dosing achieves ≥70% success in preventing mineralocorticoid excess, whereas once-daily 5 mg dosing fails in the majority of patients 4
• Never reduce to once-daily prednisone 5 mg—this subtherapeutic approach leaves patients vulnerable to dangerous hypertension and hypokalemia 4

Alternative Glucocorticoid Options

• Prednisolone 5 mg twice daily is an acceptable substitute for prednisone in patients who cannot tolerate prednisone 4
• Methylprednisolone 4 mg twice daily may be used only with the fine-particle 500 mg abiraterone formulation (not the standard 1,000 mg formulation) 1, 4
• Dexamethasone 1 mg once daily can be considered when switching from prednisone at disease progression to potentially extend response (median PFS 10.35 months in the SWITCH study) 1

Mandatory Monitoring Requirements

Monthly monitoring during the first 3 months, then regularly thereafter, must include: 1, 4

• Blood pressure: Hypertension occurs in 22% (severe in 4%); manage aggressively to prevent cardiovascular events 1
• Serum potassium: Hypokalemia in 17%; supplement as needed and consider mineralocorticoid receptor antagonists (eplerenone) for refractory cases 1, 5
• Serum phosphate: Hypophosphatemia in 24% 1
• Liver enzymes (ALT/AST) and bilirubin: Elevations lead to discontinuation in 11-12%; interrupt treatment if ALT/AST >5× ULN or bilirubin >3× ULN 1, 2
• Cardiac assessment: Atrial fibrillation in 4%, cardiac disorders in 19% (serious in 6%); symptom-directed evaluation especially in patients with pre-existing cardiovascular disease 1, 4

Critical Pitfalls to Avoid

• Do not discontinue prednisone to avoid steroid side effects without adding alternative mineralocorticoid blockade—this exposes patients to life-threatening hypertensive crises and hypokalemia 4
• Do not use methylprednisolone with the standard 1,000 mg abiraterone formulation—the two formulations have different FDA-approved steroid partners and are not interchangeable 4, 6
• Do not split abiraterone to twice-daily dosing—this doubles fasting requirements, reduces compliance, and has no supporting pharmacokinetic or efficacy data 4

Addressing Bone Pain Specifically

• Abiraterone with prednisone significantly improved time to pain progression and pain palliation in both the post-docetaxel (COU-AA-301) and pre-docetaxel (COU-AA-302) trials 1
• For patients with significant bone pain requiring narcotics, consider concurrent palliative radiotherapy or radium-223 (if appropriate), as abiraterone's analgesic effect may take weeks to manifest 1
• The prednisone component itself provides modest anti-inflammatory benefit that may help with bone pain, but the primary goal is mineralocorticoid blockade 7

Long-Term Glucocorticoid Safety Considerations

• The 10 mg/day prednisone dose is considered physiologic glucocorticoid replacement rather than pharmacologic immunosuppression 7
• Glucocorticoid-related adverse events (bone loss, hyperglycemia, immunosuppression, mood changes) are dose-dependent and typically occur at higher doses or longer durations than used with abiraterone 7
• In the LATITUDE trial (median follow-up 51.8 months), corticosteroid-associated adverse events occurred in 25.5% with abiraterone plus prednisone vs 23.3% with placebo plus prednisone, demonstrating acceptable long-term tolerability 8, 9
• The survival benefit (median OS 53.3 vs 36.5 months, HR 0.66, P<0.0001 in high-risk metastatic disease) far outweighs the modest glucocorticoid-related risks 9