RESUMO
BACKGROUND: For stage II and III head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy alone, loco-regional recurrence is the main cause of treatment failure. Strategies to improve loco-regional control should not be at the expense of increased late normal tissue toxicity. We investigated dose-intensified hypofractionated intensity-modulated radiotherapy (IMRT) with synchronous cetuximab. MATERIAL AND METHODS: In a phase I/II trial, 27 patients with stage III or high risk stage II HNSCC were recruited. They received three dose level simultaneous integrated boost IMRT, 62.5 Gy in 25 daily fractions to planning target volume one over five weeks with synchronous cetuximab. The primary endpoint was acute toxicity. Secondary endpoints included: late toxicity and quality of life; loco-regional control, cause-specific and overall survival. RESULTS: Radiotherapy was completed by 26/27 patients; for one (4%) the final fraction was omitted due to skin toxicity. All cycles of cetuximab were received by 23/27 patients. Grade 3 acute toxicities included: pain (81%), oral mucositis (78%) and dysphagia (41%). There were few grade 3 physician-recorded late toxicities, including: pain (11%), problems with teeth (8%) and weight loss (4%). At 12 months, only one (4%) patient required a feeding tube, inserted prior to treatment due to dysphagia. The maximal/peak rates of patient-reported late toxicities included: severe pain (11%), any dry mouth (89%) and swallowing dysfunction that required a soft/liquid diet (23%). At 12 months, all quality of life and most symptoms mean scores had resolved to baseline or were only a little worse; dry mouth, sticky saliva and dentition scores remained very much worse. At a median follow-up of 47 months, there were five (18.5%) loco-regional recurrences and the overall cause-specific survival was 79% (95% CI 53-92). CONCLUSIONS: This regimen is safe with acceptable acute toxicity, low rates of late toxicity and impact on quality of life at 12 months following treatment. Further evaluation is recommended.