In the TAX 323 (EORTC 24971) phase III trial enrolling patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), the addition of docetaxel (T) to cisplatin and 5-fluorouracil (PF)-based induction chemotherapy prior to definite radiotherapy significantly improved progression-free survival (PFS) and overall survival (OS). The data were updated for PFS, OS and treatment-related long-term side-effects. Baseline clinical and laboratory data of 17 variables were collected and subjected to univariate and multivariate prognostic factor analyses for OS. All 358 patients randomised between 1999 and 2002 were included in the long-term analysis with a median follow-up of 8.6 years. The primary end-point of PFS remained significantly improved with TPF compared with PF (adjusted hazard ratio [HR], 0.70; 95% CI, 0.56–0.88, p = 0.002), translating into a persisting benefit in OS (adjusted HR, 0.75; 95% CI, 0.60–0.95, p = 0.015). Long-term side-effects in the TPF/PF arms comprised tracheostomy (7%/5%), feeding tube dependency (3%/6%) and gastrostomy (11%/11%). Second malignancy occurred in 8%/3%, respectively. Out of 177 patients randomised to the TPF arm, 160 were included in the multivariate analysis. Grade 2 or more dysphagia (p = 0.002) and grade 2 or more pain (p = 0.004) at baseline were identified as independent negative prognostic factors. In addition, OS differed across primary tumour sites (p = 0.027) and was worse in patients with a higher N-stage (p = 0.025). In LA-SCCHN patients treated with sequential chemoradiotherapy, TPF induction chemotherapy demonstrated long-lasting efficacy, superior to the PF regimen. Higher-grade dysphagia and pain are unfavourable prognosticators. • TPF is the optimal induction chemotherapy before definitive locoregional treatment. • The survival benefit of TPF over PF was confirmed at median follow-up of 8.6 years. • Baseline symptoms have independent negative prognostic value for overall survival. • Overall survival depends on primary site (worse for hypopharynx and oral cavity). • Overall survival is also worse in patients with a higher nodal stage. [ABSTRACT FROM AUTHOR]