This study was designed to determine if long-term palliation could be obtained in pre-irradiated locoregional recurrent squamous head and neck cancer patients, with the administration of simultaneous chemoradiotherapy. Mandatory eligibility criteria were histologically documented squamous head and neck cancer in previously irradiated territory, surgical or brachytherapy salvage unfeasibility, or patient refusal. The protocol consisted of radiotherapy, at a rate of 5 daily fractions of 2 Gy on alternate weeks, with simultaneous continuous intravenous infusion of 5-fluorouracil (5FU) at 800 mg/m2 and oral hydroxyurea (HU) at 1,000-1,500 mg/day for 5 days. Tolerance was good. Acute toxicity was low with no grade > or = III WHO hematologic toxicity observed. Nine patients had grade III mucositis, one had grade IV, three had grade III skin toxicity, and only four patients required a 20% to 30% 5FU dose reduction because of it. Two patients had hand and foot syndrome, and two had asymptomatic 5FU-related cardiac signs (1 ECG, 1 echographic+ECG). Chronic radiotherapy-related effects consisted of Hermitte's sign observed in two patients. Of 34 registered patients, 33 were evaluable for response. An overall rate of 55% (18 patients) of objective responses [complete response (CR) + partial response (PR)] was obtained, with 12 patients (36%) achieving local control of disease. The median survival was 11 months. These data show that palliation could be obtained for the majority of responding patients, and also suggest an improvement in the immediate prognosis with this type of salvage procedure for a selected group of recurrent squamous head and neck cancer patients.