Background A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy.

Methods We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival.

For patients who were randomly assigned to receive TPF, docetaxel (at a dose of 75 mg per square meter of body-surface area) was administered as a 1-hour intravenous infusion, followed by intravenous cisplatin (100 mg per square meter), administered during a period of 0.5 to 3 hours. After completion of the cisplatin infusion, fluorouracil (1000 mg per square meter per day) was administered as a continuous 24-hour infusion for 4 days. Patients in the PF group received intravenous cisplatin (100 mg per square meter), followed by fluorouracil (1000 mg per square meter per day) as a continuous 24-hour infusion for 5 days. Induction chemotherapy was given every 3 weeks for three cycles, unless there was disease progression, unacceptable toxic effects, withdrawal of consent by the patient, or a reduction of less than 25% in tumor size after cycle 2. Patients in the TPF group were given dexamethasone to prevent docetaxel-related hypersensitivity reactions, skin toxic effects, and fluid retention and were given prophylactic antibiotics starting on day 5 of each cycle for 10 days. Primary prophylaxis with recombinant granulocyte colony-stimulating factor was not permitted.

            Chemoradiotherapy

All patients were assigned to receive chemoradiotherapy beginning 3 to 8 weeks after the start of the third cycle of induction chemotherapy (day 22 to day 56 of cycle 3). Weekly carboplatin at an area under the curve of 1.5 was given as an intravenous infusion during a 1-hour period for a maximum of seven weekly doses during the course of radiotherapy.

The definitive curative radiation dose administered to the primary tumor was between 70 and 74 Gy, administered as fractions of 2 Gy per day 5 days per week. The dose administered to uninvolved lymph nodes was at least 50 Gy. Involved lymph nodes were to receive 60 to 74 Gy, depending on whether an elective neck dissection was indicated after completion of treatment. Quality assurance for radiotherapy involved central review at both the initiation and the completion of such treatment.

            Surgery

Surgery was performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy. Surgery was also allowed for patients who did not complete chemoradiotherapy and had resectable residual disease at the primary site or in the neck.