What is the recommended treatment regimen for a patient with hormone-sensitive metastatic prostate cancer, specifically using leuprolide (Lupron), docetaxel (Taxotere), and prednisone?

Treatment Regimen for Hormone-Sensitive Metastatic Prostate Cancer with Leuprolide, Docetaxel, and Prednisone

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), the recommended regimen is leuprolide (or another ADT agent) combined with docetaxel 75 mg/m² every 3 weeks for 6 cycles plus prednisone 5 mg twice daily, which provides a survival benefit of 13.6-22 months compared to ADT alone. 1

Patient Selection Criteria

This triplet regimen is most strongly recommended for:

• Patients with de novo metastatic disease (newly diagnosed at metastatic stage) 1
• Patients with high-volume disease defined as ≥4 bone metastases with ≥1 outside the spine/pelvis, OR any visceral metastases 1
• Patients who are fit enough to tolerate chemotherapy 1

For low-volume disease patients, the evidence is less compelling—CHAARTED showed no overall survival benefit (HR 0.63,95% CI 0.34-1.17), so docetaxel should not be routinely offered to this subgroup 1

Specific Dosing Protocol

Docetaxel administration:

• 75 mg/m² intravenously every 21 days 1
• Total of 6 cycles (18 weeks of treatment) 1
• Can be given alone (per CHAARTED) or with prednisone/prednisolone (per STAMPEDE) 1

Prednisone dosing:

• 5 mg orally twice daily 1
• Continue throughout docetaxel treatment 1

Leuprolide (ADT) administration:

• Continue indefinitely to maintain castrate testosterone levels <50 ng/dL 1
• Standard depot formulations (monthly or 3-monthly) are appropriate 1

Expected Outcomes

The survival benefit is substantial in appropriate patients:

• CHAARTED trial: median overall survival 57.6 months vs 44.0 months (13.6-month gain) 1, 2
• STAMPEDE trial: 22-month survival advantage 3, 4
• Hazard ratio for death: 0.61-0.63 in high-volume disease 1

Toxicity Management

Most common grade 3-4 adverse events to monitor:

• Neutropenia (32% with 3-weekly schedule) 1, 5
• Febrile neutropenia 4
• Fatigue/asthenia 1, 5
• Peripheral neuropathy 1, 5
• Diarrhea 1, 5
• Alopecia (expected but not dose-limiting) 1, 5

Alternative Considerations

If chemotherapy is contraindicated or patient declines docetaxel, the alternative standard of care is ADT plus abiraterone 1,000 mg daily with prednisone 5 mg daily, which provides similar survival benefits across all disease volumes 1. Other options include ADT plus apalutamide or ADT plus enzalutamide 1.

The ESMO guidelines note that ADT plus docetaxel plus abiraterone plus prednisone (quadruplet therapy) is recommended for fit patients with de novo mHSPC, especially those with multiple bone metastases or visceral disease, though this regimen is not yet FDA/EMA approved for M0 disease. 1

Critical Pitfalls to Avoid

• Do not use docetaxel in low-volume disease patients—the survival benefit is not established 1
• Do not use ADT alone in patients fit for combination therapy—this represents suboptimal treatment 1
• Do not stop ADT after completing docetaxel—androgen suppression must continue indefinitely 1
• Do not delay treatment initiation—the strongest evidence supports upfront combination therapy rather than sequential approaches 1

Monitoring Requirements

• PSA levels every 3 months 1
• Testosterone verification to confirm castrate levels (<50 ng/dL) 1
• Complete blood counts before each docetaxel cycle 5
• Clinical assessment for neuropathy, fatigue, and quality of life 1