Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan. Issue 5 (October 2018) - Matsuyama, Hiroshi
Abstract: Objective: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100 mg/m 2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. Methods: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II–IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70 mg/m 2 for level 0, 80 mg/m 2 for level 1, and 100 mg/m 2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200 mg/m 2, response rate, and incidences of adverse events. Results: A CDDP dose of 100 mg/m 2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m 2 . Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200 mg/m 2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. Conclusion: The present phase I study indicated that a CDDP dose of 80 mg/m 2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80 mg/m 2 as compared with a dose of 100 mg/m 2, and a dose of 80 mg/m 2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).