What are alternative treatment options to abiraterone (Zytiga) and prednisone with spironolactone (Aldactone) for metastatic castration-resistant prostate cancer?

Alternative Treatment Options to Abiraterone and Prednisone with Spironolactone for Metastatic Castration-Resistant Prostate Cancer

For patients taking abiraterone with prednisone who cannot use spironolactone, enzalutamide is the preferred alternative treatment option for metastatic castration-resistant prostate cancer (mCRPC). 1

Reason for Avoiding Spironolactone with Abiraterone

• Spironolactone should be avoided when taking abiraterone because spironolactone is a mineralocorticoid receptor antagonist that can interfere with abiraterone's mechanism of action and potentially reduce its efficacy 1
• Abiraterone requires concurrent steroid (prednisone or methylprednisolone) to manage mineralocorticoid excess side effects including hypertension, hypokalemia, and peripheral edema 1

Primary Alternative Treatment Options

Enzalutamide

• First-line alternative to abiraterone for mCRPC with strong evidence supporting its use 1
• Recommended dose is 160 mg per day 1
• Does not require concurrent steroid administration 1
• Potential side effects include fatigue, hypertension, and rarely seizures 1

Docetaxel-based Chemotherapy

• Standard treatment option for mCRPC patients with good performance status who have progressed on hormonal therapy 1
• Particularly appropriate for patients with symptomatic disease or visceral metastases 1
• Should be considered when rapid response is needed due to high symptom burden 1

Cabazitaxel

• Recommended for patients who have received prior docetaxel chemotherapy 1
• Particularly useful if patient previously received abiraterone prior to docetaxel 1
• Associated with higher rates of neutropenia and diarrhea than docetaxel 1

Other Treatment Options

Radium-223

• Specifically indicated for patients with symptomatic bone metastases without known visceral disease 1
• Can be used in patients with good performance status who have not received prior docetaxel 1
• Improves overall survival while targeting bone metastases 1

Ketoconazole plus Steroid

• Alternative option for patients with mCRPC with good performance status when preferred agents are unavailable 1
• Lower efficacy compared to newer androgen-targeted therapies but may provide clinical benefit 1
• Requires monitoring for liver toxicity and adrenal insufficiency 1

Fine-particle Formulation of Abiraterone

• Alternative formulation that can be used with methylprednisolone instead of prednisone 1
• Bioequivalent at 500 mg to 1,000 mg of the original formulation 1
• May be considered as a category 2B option according to NCCN guidelines 1

Treatment Selection Algorithm

1. First-line treatment decision:

   • If patient cannot take abiraterone + prednisone with spironolactone:
     • Enzalutamide (preferred) 1
     • Docetaxel (if symptomatic or rapid progression) 1

2. Second-line treatment decision:

   • If progression after enzalutamide:
     • Docetaxel chemotherapy 1
     • Cabazitaxel (if prior docetaxel) 1
   • If bone-predominant metastases:
     • Consider Radium-223 1

3. Third-line treatment decision:

   • Cabazitaxel (if not used previously and after docetaxel) 1
   • Clinical trial enrollment 1
   • Ketoconazole + steroid (if other options exhausted) 1

Important Monitoring Considerations

• Regular monitoring of liver function, potassium levels, and blood pressure is essential with all hormonal therapies 1
• Cardiac monitoring is particularly important in patients with pre-existing cardiovascular disease 1
• PSA response should be evaluated regularly but treatment decisions should not be made solely on PSA changes 1

Common Pitfalls to Avoid

• Avoid switching between abiraterone formulations upon disease progression 1
• Do not use abiraterone with either steroid following progression on abiraterone with the other steroid 1
• Avoid concurrent use of enzalutamide with abiraterone due to drug-drug interactions that increase abiraterone clearance and toxicity without significant survival benefit 2
• Do not use sipuleucel-T in symptomatic mCRPC patients with poor performance status 1