Phase I trial of concomitant hyperfractionated radiotherapy with docetaxel and cisplatin for locally advanced head and neck cancer

BACKGROUND This study was conducted to determine the maximum tolerated dose of docetaxel when administered concomitantly with radical hyperfractionated radiotherapy and cisplatin in patients with locally advanced head and neck cancer. PATIENTS AND METHOD Patients with stage III-IV tumors received radical radiotherapy of 74.4 Gy given in two daily fractions of 1.2 Gy for 6 weeks. Cisplatin was given once weekly on day 1 at a constant dose of 15 mg/m(2). The starting dose of docetaxel was 10 mg/m(2) once weekly on day 3, with planned escalation steps of 5 mg/m(2). Main endpoints of the study were the maximum tolerated dose of docetaxel, acute toxicities, and the preliminary efficacy results. RESULTS Twenty-five patients were enrolled. Median follow-up was 15 months (range: 4-40 months). Two of three patients presented with dose-limiting toxicities at the 15-mg/m(2) dose of docetaxel (one patient presented with multiple grade 3-4 toxicities requiring hospitalization for management and another presented with multiple toxicities including life-threatening bronchotranspiration). Thus, the weekly docetaxel dose of 10 mg/m(2) was considered the maximum tolerated dose. Nineteen patients were then treated with the maximum tolerated dose and no dose-limiting toxicities were observed. Radiotherapy was completed in all patients except one (median dose: 74.4; range: 73.2-74.4), and at least 80% of the scheduled cisplatin and docetaxel doses were given in 92% of the patients. Acute toxicities were dominated by grade 3 mucositis (92%) and grade 3-4 dysphagia (68%). The 2.5-year actuarial local control rate was 87.5%, and the disease-free survival rate was 75%. At the time of last follow-up, 23 patients were alive and two had died from cancer. No distant metastases were observed. DISCUSSION In patients with locally advanced head and neck cancer, this study determined the maximum tolerated dose of docetaxel to be 10 mg/m(2) administered once weekly when given concurrently with 74.4 Gy hyperfractionated radiotherapy and a weekly 15-mg/m(2) dose of cisplatin. The toxicity profile and the encouraging results suggest that this new combination merits further investigation in a multi-institutional phase II trial.