Background
Phase III, open-label RCT. 1006 patients with metastatic castration-resistant prostate cancer (mCRPC) with disease progression on castration therapy. Prior chemotherapy not allowed. Compared three-weekly docetaxel versus weekly docetaxel versus mitoxantrone + prednisone (standard of care at the time). Three-weekly docetaxel arm was the primary experimental arm.
Interventions and follow up
Arm A: Docetaxel 75mg/m² IV q3wk + prednisone 5mg twice daily (n=335)
Arm B: Docetaxel 30mg/m² IV weekly × 5 of 6 wk + prednisone 5mg twice daily (n=334)
Arm C: Mitoxantrone 12mg/m² IV q3wk + prednisone 5mg twice daily (control, n=337)
Primary endpoint: Overall survival (OS)
mFollow up: Minimum 13.5 mo (primary); updated at 2 yr
Arm B: Docetaxel 30mg/m² IV weekly × 5 of 6 wk + prednisone 5mg twice daily (n=334)
Arm C: Mitoxantrone 12mg/m² IV q3wk + prednisone 5mg twice daily (control, n=337)
Primary endpoint: Overall survival (OS)
mFollow up: Minimum 13.5 mo (primary); updated at 2 yr
Results
OS (Arm A vs Arm C): 18.9 vs 16.5 mo, HR 0.76, P=.009
OS (Arm B vs Arm C): 17.4 vs 16.5 mo, HR 0.91, P=.36 — not significant
PSA response (≥50% decline, Arm A): 45% vs 32% (Arm C)
Pain response (Arm A): 35% vs 22% (Arm C)
OS (Arm B vs Arm C): 17.4 vs 16.5 mo, HR 0.91, P=.36 — not significant
PSA response (≥50% decline, Arm A): 45% vs 32% (Arm C)
Pain response (Arm A): 35% vs 22% (Arm C)
Adverse events
Hematologic: Febrile neutropenia 3% (Arm A)
Constitutional / gastrointestinal: Fatigue 3%; nausea/vomiting 2% (Arm A, grade ≥3)
Neurologic: Peripheral neuropathy 2%; sensory neuropathy 2% (Arm A, grade ≥3)
Cardiac: Cardiac toxicity lower with docetaxel than with mitoxantrone
Treatment discontinuation: 18% (Arm A) vs 9% (Arm C)
Constitutional / gastrointestinal: Fatigue 3%; nausea/vomiting 2% (Arm A, grade ≥3)
Neurologic: Peripheral neuropathy 2%; sensory neuropathy 2% (Arm A, grade ≥3)
Cardiac: Cardiac toxicity lower with docetaxel than with mitoxantrone
Treatment discontinuation: 18% (Arm A) vs 9% (Arm C)
Conclusions
Three-weekly docetaxel + prednisone significantly prolonged OS versus mitoxantrone + prednisone in mCRPC, establishing docetaxel as the first chemotherapy agent to improve survival in this disease. Weekly docetaxel did not significantly improve OS. This trial defined the mCRPC chemotherapy standard for a decade.
Key Limitations
Key Limitations: Mitoxantrone is a weak comparator — its approval was based on palliative endpoints rather than survival, and it has no OS benefit. The survival benefit of 2.4 months median OS is modest, though the HR of 0.76 represents a real but incremental effect. Patients were unselected — no androgen receptor or DNA repair biomarkers used. Corticosteroid co-administration (prednisone) provides independent palliative benefit, making it difficult to isolate docetaxel's contribution. TAX 327 predates PSA-ARPI-era mCRPC treatment, and docetaxel today is typically used after one or more ARPIs.
Clinical Context
TAX 327 and SWOG 9916 (Petrylak DP, NEJM 2004) together established docetaxel + prednisone as the mCRPC standard, garnering FDA approval in 2004. Docetaxel was the first therapy to demonstrate an OS benefit in mCRPC, a landmark achievement at the time. In the modern treatment landscape, docetaxel is typically used after progression on one or two ARPIs; cabazitaxel (CARD) is preferred in the post-ARPI + docetaxel setting.
References
References: Tannock IF et al, NEJM 2004