Background
Phase III, open-label RCT (TAX 323/EORTC 24971). 358 patients aged 18-70 with unresectable stage III or IV locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) without distant metastases. Nasopharynx and nasal/paranasal primaries excluded. Tested addition of docetaxel to cisplatin + fluorouracil induction chemotherapy prior to definitive radiotherapy.
Interventions and follow up
Arm A (TPF): Docetaxel 75 mg/m² IV day 1 + cisplatin 75 mg/m² IV day 1 + 5-FU 750 mg/m²/day continuous infusion days 1-5, q3wk × 4 cycles, followed by radiotherapy 66-70 Gy (no concurrent chemotherapy)
Arm B (PF): Cisplatin 100 mg/m² IV day 1 + 5-FU 1000 mg/m²/day continuous infusion days 1-5, q3wk × 4 cycles, followed by the same radiotherapy
Primary endpoint: Progression-free survival (PFS)
mFollow up: 32.5 months
Arm B (PF): Cisplatin 100 mg/m² IV day 1 + 5-FU 1000 mg/m²/day continuous infusion days 1-5, q3wk × 4 cycles, followed by the same radiotherapy
Primary endpoint: Progression-free survival (PFS)
mFollow up: 32.5 months
Results
mPFS: 11.0 vs 8.2 months (TPF vs PF), HR 0.72, 95%CI 0.57-0.91, P=.007
mOS: 18.8 vs 14.5 months, HR 0.73, 95%CI 0.56-0.94, P=.02 (27% reduction in risk of death with TPF)
3-yr OS: 37% vs 26% (TPF vs PF)
mOS: 18.8 vs 14.5 months, HR 0.73, 95%CI 0.56-0.94, P=.02 (27% reduction in risk of death with TPF)
3-yr OS: 37% vs 26% (TPF vs PF)
Adverse events
Hematologic (TPF vs PF): grade 3/4 neutropenia 76.9% vs 52.5%; febrile neutropenia 5.2% vs 2.8%; grade 3/4 thrombocytopenia 5.2% vs 17.9%
Non-hematologic (TPF vs PF): grade 3/4 stomatitis 0.6% vs 11.2%; alopecia 11.6% vs 0%; hearing loss 0% vs 2.8%; treatment-related death 2.3% vs 5.5%
Non-hematologic (TPF vs PF): grade 3/4 stomatitis 0.6% vs 11.2%; alopecia 11.6% vs 0%; hearing loss 0% vs 2.8%; treatment-related death 2.3% vs 5.5%
Conclusions
Induction chemotherapy with TPF significantly improved both PFS and OS compared with PF in unresectable locoregionally advanced SCCHN, with a lower rate of treatment-related mortality, establishing TPF as a superior induction regimen prior to radiotherapy.
Key Limitations
TAX 323 used radiotherapy alone after induction (no concurrent chemoradiation), which is no longer standard, limiting direct applicability to modern induction-then-concurrent-chemoradiation sequencing. The trial predates HPV status assessment and modern IMRT, and does not establish whether induction TPF adds benefit over upfront concurrent chemoradiation.
Clinical Context
Together with the companion TAX 324 trial, TAX 323 established docetaxel-based TPF as the preferred induction regimen over PF when induction chemotherapy is selected for locally advanced SCCHN. ESMO guidelines endorse TPF as the induction regimen of choice, though induction is reserved for selected patients (e.g., bulky disease, organ preservation) rather than routine use, as concurrent chemoradiation remains the definitive standard.