Phase I trial of concurrent chemoradiotherapy for laryngeal and hypopharyngeal cancers with bi-weekly docetaxel

Docetaxel (DOC) has radiation-sensitizing effects because it synchronizes with the most radiation-sensitive G2/M phase of the cell cycle. From the results of concurrent radiotherapy with weekly DOC administrations in a phase I trial, dose-limiting toxicity (DLT) was mucositis and the recommended dose was 10 mg/m2, but the administration schedule was a problem. We planned concurrent radiation therapy in a bi-weekly DOC phase I trial to improve the larynx preservation rate and to determine which schedule and dosage of DOC would yield its inherent cytotoxic effects. We decided the maximum tolerated dose (MTD) and DLT to serve as an index of the appearance of adverse events. Patients with stage II or stage III T2N1 hypopharyngeal cancer or stage II or III laryngeal cancer were included in this study. DOC was administered on the days of initiation of bi-weekly radiation (day 1, day 15, day 29). Radiation was given (2 Gy/day: 5 days per week) for a total of 30 Fr, with a total of 60 Gy. The starting dose of DOC was 30 mg/m2 (level 1) and the dosage was raised by 5 mg/m2 at each level. DLT was observed due to mucositis and neutropenia at 40 mg/m2 (level 3), the MTD was 40 mg/m2 and the recommended dose (RD) was 35 mg/m2. Especially in hypopharyngeal cancer of Grade 3 or more, mucositis appeared, with swallowing difficulty in cases with a wide range of irradiation. At dosages of 35 mg/m2, the effectiveness was favorable and this was the suitable dosage recommended for the subsequent phase II trial. This clinical study was performed with permission of our IRB (Institutional Review Board). (author)