In a patient with castration‑sensitive prostate cancer, is the preferred first‑line docetaxel regimen the standard 75 mg/m² every 3 weeks schedule or a weekly dosing schedule?

Docetaxel Dosing in Castration-Sensitive Prostate Cancer

Direct Recommendation

For castration-sensitive prostate cancer, the standard and preferred docetaxel regimen is 75 mg/m² every 3 weeks for 6 cycles, not a 2-weekly schedule. 1

Evidence-Based Rationale

Standard Regimen for Castration-Sensitive Disease

The evidence for docetaxel in castration-sensitive prostate cancer is exclusively based on the every 3-week schedule at 75 mg/m²:

• CHAARTED trial established docetaxel 75 mg/m² every 3 weeks for 6 cycles plus ADT as standard, demonstrating improved overall survival (57.6 vs 47.2 months; HR 0.72; P=0.002) 1
• STAMPEDE trial confirmed this survival benefit using the identical 3-weekly regimen (median OS 5.4 years vs 3.6 years with ADT alone) 1
• Both pivotal trials used specifically 6 cycles of the 3-weekly regimen 1

The 2-Weekly Schedule Context

The 2-weekly docetaxel regimen (50 mg/m²) has only been studied in castration-resistant prostate cancer (CRPC), not castration-sensitive disease:

• A phase II trial in 346 patients with metastatic CRPC showed 2-weekly dosing had improved tolerability with febrile neutropenia rates of 4% vs 14% 1
• This schedule showed longer median survival (19.5 vs 17.0 months; P=0.015) in the CRPC setting only 1
• No trials have evaluated 2-weekly docetaxel in castration-sensitive prostate cancer 2, 3

Critical Clinical Distinction

You cannot extrapolate CRPC dosing data to the castration-sensitive setting because:

• The treatment goals differ fundamentally (curative intent vs palliative in CRPC) 1
• The disease biology and treatment duration are different (6 fixed cycles vs treatment until progression) 1
• Triplet therapy combinations (ADT + docetaxel + abiraterone/darolutamide) showing superior outcomes all used the 3-weekly schedule 1

When 2-Weekly Dosing May Be Considered

The 2-weekly schedule is only appropriate for castration-resistant disease in specific circumstances:

• Older, frailer patients with higher ECOG performance status and comorbidities 3
• Patients at high risk for febrile neutropenia or severe toxicity 2, 3
• Never as first-line in castration-sensitive disease 1

Common Pitfalls to Avoid

• Do not use 2-weekly dosing in castration-sensitive disease simply because it appears better tolerated—there is zero evidence supporting efficacy in this setting 1
• Do not reduce the planned 6 cycles in castration-sensitive disease unless toxicity mandates it, as the trials establishing benefit used this specific duration 1
• Do not confuse CRPC data with castration-sensitive data—these are fundamentally different disease states with different evidence bases 1
• Recognize that current guidelines no longer recommend docetaxel alone for castration-sensitive disease; triplet therapy (docetaxel + novel hormonal agent) is now preferred for high-volume disease 1