In a 76‑year‑old man with metastatic prostate cancer on androgen‑deprivation therapy receiving low‑dose abiraterone 250 mg once daily, should prednisolone be given 5 mg once daily or 10 mg daily (5 mg twice daily)?

Prednisolone Dosing with Low-Dose Abiraterone 250 mg

When using low-dose abiraterone 250 mg once daily with food, prednisolone should be given at 5 mg twice daily (total 10 mg/day), not 5 mg once daily. 1, 2

Standard Glucocorticoid Requirement

• The mandatory glucocorticoid dose remains prednisone 5 mg twice daily (or prednisolone 5 mg twice daily) regardless of whether you use standard-dose abiraterone 1,000 mg fasted or low-dose abiraterone 250 mg with food. 1, 2

• The glucocorticoid requirement is driven by abiraterone's CYP17A1 inhibition, which causes mineralocorticoid excess (hypertension in ~22%, hypokalemia in ~17%, peripheral edema in ~28%), and this mechanism is independent of the abiraterone dose. 1, 2

• Do not reduce prednisolone to 5 mg once daily—twice-daily dosing achieves ≥70% success in preventing mineralocorticoid excess, whereas once-daily dosing fails in the majority of patients. 2

Evidence for Low-Dose Abiraterone Regimen

• The NCCN phase II noninferiority study that validated 250 mg abiraterone with a low-fat breakfast used the same prednisone dose of 5 mg twice daily as the standard 1,000 mg fasted regimen. 1

• This low-dose approach (250 mg with food plus prednisone 5 mg twice daily) demonstrated noninferior PSA response (58% vs 50%) and equal progression-free survival (9 months in both arms) compared to standard dosing. 1

Critical Monitoring Requirements

• Monthly monitoring during the first three months is mandatory, then at regular intervals, including: 2
  • Blood pressure (hypertension in ~22% of patients, severe in 4%) 2
  • Serum potassium (hypokalemia in ~17%) 2
  • Serum phosphate (hypophosphatemia in ~24%) 2
  • Liver enzymes (ALT/AST) (elevations leading to discontinuation in 11-12%) 2
  • Cardiac assessment for those with pre-existing cardiovascular disease (atrial fibrillation in 4%, cardiac disorders in 19%) 2

Important Clinical Caveats

• The low-dose 250 mg regimen with food is Category 2B and should only be considered when patients cannot afford or will not take standard dosing; food impacts absorption unpredictably, requiring vigilant monitoring for excess toxicity. 1

• If mineralocorticoid excess develops despite twice-daily prednisolone, add mineralocorticoid receptor antagonists (e.g., eplerenone) rather than discontinuing the glucocorticoid. 2

• Standard dosing (1,000 mg fasted) should be resumed if excess toxicity is observed on the modified 250 mg with food regimen. 1