What is Abiraterone and Its Clinical Uses
Abiraterone acetate is an irreversible CYP17 enzyme inhibitor that blocks androgen biosynthesis and is FDA-approved in combination with prednisone for treating metastatic castration-resistant prostate cancer (mCRPC), demonstrating significant survival benefits in both chemotherapy-naïve and post-docetaxel settings. 1
Mechanism of Action
Abiraterone acetate works by irreversibly inhibiting the 17α-hydroxylase and C17,20-lyase enzymatic activities of cytochrome P450 17A (CYP17A), which is essential for androgen biosynthesis in the adrenal glands, testes, and prostate tumor tissue itself 2. This mechanism effectively suppresses testosterone production throughout the body, depriving prostate cancer cells of critical growth signals even after they have developed resistance to standard androgen deprivation therapy 3, 4.
FDA-Approved Indications
Abiraterone acetate is indicated exclusively for metastatic castration-resistant prostate cancer in combination with prednisone. 1 The drug has demonstrated efficacy in two distinct clinical scenarios:
Post-Docetaxel Setting
- Median overall survival improved from 10.9 months (placebo) to 14.8 months with abiraterone (HR 0.65; 95% CI 0.54-0.77; p<0.0001) 3
- Significant improvements in radiographic progression-free survival, time to PSA progression, and pain palliation 2
Chemotherapy-Naïve (Pre-Docetaxel) Setting
- Radiographic progression-free survival improved from 8.3 months to 16.5 months (HR 0.53; p<0.001) 2, 3
- Overall survival improved from 30.3 months to 34.7 months at final analysis (HR 0.81; 95% CI 0.70-0.93; p=0.003) 2
- PSA declines >50% occurred in 62% vs 24% with placebo 2
- Significant delays in time to symptomatic deterioration, chemotherapy initiation, and pain progression 2
Dosing and Administration
The standard dose is 1,000 mg orally once daily taken on an empty stomach (at least 1 hour before or 2 hours after food) in combination with prednisone 5 mg twice daily. 1, 2 This fasting requirement is critical—taking abiraterone with food significantly increases drug absorption and may result in adverse reactions 1.
Alternative Dosing Strategy
- A fine-particle formulation at 500 mg daily with methylprednisolone 4 mg twice daily is bioequivalent to the standard formulation and FDA-approved 2
- An alternative strategy of 250 mg daily with a low-fat breakfast may reduce financial toxicity while maintaining efficacy 2, 5
- Do not switch between formulations at disease progression—this provides no clinical benefit 2
Dose Modifications
- For baseline moderate hepatic impairment (Child-Pugh Class B): reduce starting dose to 250 mg once daily 1
- For hepatotoxicity during treatment: hold therapy until recovery, then may restart at reduced dose 1
Mandatory Concurrent Therapy
Abiraterone must always be given with concurrent corticosteroids (prednisone 5 mg twice daily or methylprednisolone 4 mg twice daily) to prevent mineralocorticoid excess. 2, 1 Without corticosteroids, CYP17A inhibition causes upstream accumulation of mineralocorticoid precursors, leading to hypertension, hypokalemia, and fluid retention 2.
Patients must also continue androgen deprivation therapy (GnRH analog or bilateral orchiectomy) throughout abiraterone treatment. 1
Adverse Effects and Monitoring Requirements
Common Adverse Reactions (>10%)
- Fatigue (39%), arthralgia, back/joint discomfort (28-32%) 2
- Hypertension (22%, severe in 4%), peripheral edema (28%) 2
- Hypokalemia (17%), hypophosphatemia (24%) 2
- Gastrointestinal: diarrhea, nausea, constipation (22%) 2
- Hot flushes (22%), urinary tract infections 2
Serious Adverse Effects Requiring Monitoring
Monthly monitoring (at minimum initially) must include: 2, 5
- Blood pressure measurements
- Serum potassium and phosphate levels
- Liver function tests (AST/ALT)
- Symptom assessment for fluid retention and cardiac disease 2
Critical Safety Warnings
Hepatotoxicity: Can be severe and fatal; 11-12% of patients discontinued therapy due to elevated liver enzymes 2, 1
Cardiovascular toxicity: 19% experienced cardiac disorders (6% serious), including atrial fibrillation (4%) 2. Particularly important in patients with pre-existing cardiovascular disease 2.
Hypoglycemia: Severe hypoglycemia reported in diabetic patients taking thiazolidinediones or repaglinide—monitor blood glucose closely and adjust antidiabetic medications as needed 1
Contraindication with radium-223: Combination therapy showed increased mortality and fracture rates—this combination is not recommended 1, 5
Place in Treatment Algorithm
For asymptomatic or minimally symptomatic mCRPC patients with good performance status who are chemotherapy-naïve, abiraterone plus prednisone is a Category 1 standard treatment option alongside docetaxel and sipuleucel-T. 2, 5, 6
For symptomatic mCRPC patients post-docetaxel, abiraterone plus prednisone remains a standard option if not previously used. 6 However, cabazitaxel is preferred as second-line chemotherapy after docetaxel failure rather than switching between novel hormone therapies 6.
Treatment Selection Considerations
- Abiraterone is particularly appropriate for patients preferring oral therapy over intravenous chemotherapy 2
- The side effect profile may be more favorable than docetaxel for patients concerned about chemotherapy toxicity 2
- Not appropriate for patients with severe baseline hepatic impairment 1
Critical Pitfalls to Avoid
Do not administer abiraterone with food—this dramatically increases drug exposure and toxicity risk 1
Never omit concurrent corticosteroids—mineralocorticoid excess can be life-threatening 2, 1
Do not combine with radium-223—increased mortality demonstrated 1
Do not use in non-metastatic CRPC outside clinical trials—no evidence of benefit in this population 2
Dose escalation at progression is ineffective—increasing to 1,000 mg twice daily at disease progression provides no clinical benefit and cannot be recommended 7