Phase I trial of chemoradiotherapy with the combination of S-1 plus cisplatin for patients with unresectable locally advanced squamous cell carcinoma of the head and neck

The aim of the present study was to determine the maximum tolerated dose (MTD) of S-1 in combination with chemoradiotherapy (CRT) in patients with unresectable locally advanced squamous cell carcinoma of the head and neck, and evaluate the difference in pharmacokinetics of S-1 when administered as a suspension via a feeding tube or orally as a capsule. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 60 and 80mg/m² per day, and cisplatin at 20mg/m² per day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70Gy in 35 fractions was given concurrently starting on day 1. Two additional cycles of chemotherapy were planned after the completion of CRT. Before starting CRT, each patient received S-1 via two different administration methods. Twenty-two patients were enrolled. The MTD was reached with S-1 at 80mg/m² per day, with two of six patients experiencing febrile neutropenia lasting more than 4days. All four patients whose creatinine clearance was decreased to <60mL/min after the first cycle of chemotherapy developed febrile neutropenia lasting more than 4days. Pharmacokinetic analysis revealed that the 5-fluorouracil area under the curve did not significantly differ by the administration route. S-1 at 60mg/m² per day for 14days was well tolerated with concurrent CRT. Administration of S-1 as a suspension or by whole capsule can be considered therapeutically interchangeable. Although these data are preliminary, activity was highly promising, and this approach warrants further investigation. (Cancer Sci 2011; 102: 419-424)