A phase I study of intra-arterial (IA) cisplatin (C) and accelerated fractionation (AF) radiotherapy (RT) for locally advanced head and neck squamous cell carcinoma (HNSCC)

Abstract

16512 Background: Concurrent IAC and conventional fractionation (CF) RT is an effective treatment for locally advanced HNSCC. AF RT with 2 late concurrent IAC doses may be equally effective since AF RT produces better local tumor control compared with CF RT and late chemotherapy boost may counteract accelerated repopulation of tumor cells. The maximum-tolerated dose (MTD) of IAC given concurrently with AF RT is not known. Methods: A phase I study was conducted in patients with locally advanced stage III/IV HNSCC to determine the MTD of C that was given as 2 selective IA infusions 1 week apart during the last 2 weeks of AF RT (70 Gy/35 fractions/6 weeks) using 6 fractions/week. IV sodium thiosulfate was used to neutralize the systemic toxicity of C. Starting at 100 mg/m2, cohorts of 3 to 6 patients were treated with escalating doses of IAC, in 25 mg/m2 increments, up to the highest level of 200 mg/m2 per infusion. Dose-limiting toxicity (DLT) was defined as the occurrence in 2 patients at a dose level of grade 3 acute mucositis or skin reactions lasting more than 8 weeks after completion of treatment; grade 4 hematologic, infective, metabolic or hearing toxicity; or grade 3 renal, hepatic or neurological toxicity. The MTD was defined as the dose level immediately lower than that resulting in DLT. Results: Ten patients were recruited with a mean age of 56 years. Two patients had stage III; 1, stage IVa; and 7, stage IVb disease. The T-stages were T1 (n = 2), T2 (n = 1), T3 (n = 2), and T4 (n = 5). The N-stages were N0 (n = 2), N1 (n = 1), N2 (n = 4), and N3 (n = 3). Three patients received IAC at a dose level of 100 mg/m2, 3 at 125 mg/m2, and 4 at 150 mg/m2. All patients had the 2 planned doses except one in the lowest dose level who developed grade 3 hyponatremia after the first dose. There was no treatment-related mortality. DLT occurred in 2 patients at the 150 mg/m2 dose level. One of them had grade 4 leukopenia, and the other had grade 3 acute skin reactions lasting 9 weeks after RT. Thus, MTD was 125 mg/m2. At a median follow-up of 24 months, 6 patients remained alive and disease-free. Conclusions: In patients with locally advanced HNSCC, AF RT with 2 doses of late IAC boost was feasible. The MTD of IAC was 125 mg/m2. No significant financial relationships to disclose.