Recommended Doses for High-Volume Metastatic Hormone-Sensitive Prostate Cancer
For high-volume metastatic hormone-sensitive prostate cancer, abiraterone should be dosed at 1,000 mg orally once daily with prednisone 5 mg once daily, while darolutamide should be dosed at 600 mg (two 300 mg tablets) orally twice daily with food. 1, 2
Abiraterone Dosing
The standard regimen is abiraterone 1,000 mg once daily with either prednisone 5 mg once daily or prednisolone 5 mg once daily until disease progression. 1
Key Dosing Details:
- Abiraterone 1,000 mg is taken as a single daily dose 1
- Must be combined with prednisone 5 mg once daily (not twice daily as used in castration-resistant disease) 1
- Continue treatment until progression to castration-resistant disease 1
- This represents a Category 1 recommendation with strong evidence from LATITUDE and STAMPEDE trials 1
Alternative Formulation:
- A fine-particle formulation at 500 mg daily (taken with food) is bioequivalent to 1,000 mg of the original formulation (taken fasting) 1
- When using the fine-particle formulation, combine with methylprednisolone 4 mg twice daily instead of prednisone 1
Critical Monitoring Requirements:
- Monitor blood pressure, potassium levels, phosphate levels, and liver function monthly, especially initially 1
- Watch for mineralocorticoid excess: hypertension (22% incidence), hypokalemia (17%), and peripheral edema (28%) 1
- Severe hypertension occurs in 4% of patients and cardiac disorders in 19% (6% serious) 1
- Grade 3-5 liver toxicity occurs in 7% of patients 1
Darolutamide Dosing
The FDA-approved dose is 600 mg (two 300 mg tablets) orally twice daily, taken with food. 2
Key Dosing Details:
- Total daily dose is 1,200 mg divided into two 600 mg doses 2
- Tablets must be swallowed whole with food 2
- When combined with docetaxel for metastatic hormone-sensitive disease, start the first docetaxel cycle within 6 weeks of initiating darolutamide 2
- Continue concurrent GnRH analog or ensure patient has had bilateral orchiectomy 2
Important Safety Considerations:
- Monitor for ischemic heart disease; optimize cardiovascular risk factors before and during treatment 2
- Discontinue for Grade 3-4 cardiac events 2
- Consider discontinuation if seizure develops during treatment 2
- Most common adverse reactions (≥10%) include constipation, rash, decreased appetite, hemorrhage, weight increase, and hypertension 2
Critical Clinical Context
For high-volume disease specifically (defined as ≥4 bone metastases with ≥1 outside spine/pelvis, and/or visceral metastases), abiraterone has the strongest evidence base. 1 The LATITUDE trial specifically enrolled high-risk patients with ≥2 of: Gleason ≥8, ≥3 bone metastases, or visceral disease, demonstrating a 38% reduction in death risk (HR 0.62). 1
Darolutamide is FDA-approved for metastatic hormone-sensitive prostate cancer in combination with docetaxel, not as monotherapy with ADT alone. 2 This is a crucial distinction—if you're considering darolutamide, you must also plan to use docetaxel chemotherapy.
Common Pitfall to Avoid:
Never switch between different androgen receptor inhibitors (abiraterone to darolutamide or vice versa) after resistance develops—this approach is rarely effective and not recommended by NCCN guidelines. 3 If progression occurs on one agent, move to a different class of therapy such as cabazitaxel chemotherapy rather than switching to another AR-targeted agent. 3
Continue ADT indefinitely to maintain castrate testosterone levels (<50 ng/dL) even during disease progression, as cancer cells remain dependent on residual androgen signaling. 4, 3