Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: Toxicities and responses

Purpose: Extrapolating from our experience delivering a "boost" field of ra diation concurrently with fields treating both gross and subclinical diseas e at the end of a course of radiation therapy, we developed a regimen to de liver concurrent chemotherapy during the last 2 weeks of a conventionally f ractionated course of radiation. Patients and Methods: Patients had stage III or IV biopsy-proven squamous c ell carcinoma originating from a head and neck mucosal sire. The regimen wa s 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisp latin given daily with each radiation dose during the last 2 weeks. A phase I study wets performed to determine the maximum-tolerated dose (MTD) befor e a phase II study was conducted. Results: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day fo r cisplatin, Mucositis persisting more than 6 weeks after therapy was the d ose-limiting toxicity. A total of 60 patients were Recited on the two phase s of the study, Eighteen patients (35%) treated at the MTD developed prolon ged mucositis, There were two cases of neutropenic sepsis, including one fa tality. The actuarial 2-year rates for overall survival, freedom from relap se, and local control were 62%, 59%, and 80%, respectively. Conclusion: Preliminary locoregional control rater seem to be higher than t hose reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliv er an intense treatment schedule, which could be completed without signific ant interruptions, and to obtain high control rater above the clavicles. Th ese end points were achieved, (C) 1999 by American Society of Clinical Onco logy.