Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma ofthe head and neck

Purpose: Paclitaxel is one of the most active agents for squamous cell carc inoma of the head and neck (SCCHN) and an in vitro radiosensitizer. The dos e-response relationship for paclitaxel may depend more on exposure duration than on peak concentration. This National Cancer Institute-sponsored phase I trial was designed to determine the feasibility of combining continuous- infusion (CI) paclitaxel with concurrent radiation therapy (RT). Patients and Methods: Patients with previously untreated stage IVA/B SCCHN were eligible. Primary end points were determination of the maximum-tolerat ed dose, dose-limiting toxicity, and pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7 weeks) during PT (70 Gy/7 weeks) . Results: Twenty-seven patients were enrolled and assessable for toxicity. N ineteen of the patients who completed greater than or equal to 70 Gy were a ssessable for response. Grade 3 skin and mucosal acute reactions occurred a t 10.5 mg/m(2)/d, but uninterrupted treatment was possible in five of six p atients. At 17 mg/m(2)/d, skin toxicity required a 2-week treatment break f or all three patients. The mean paclitaxel serum concentration at dose leve ls greater than or equal to 6.5 mg/m(2)/d exceeded that reported to achieve in vitro radiosensitization. Initial locoregional control was achieved in 14 (58%) of 24 of patients treated to 70 Gy, and control persisted in nine (38%). Conclusion: CI paclitaxel with concurrent PT is a feasible and tolerable re gimen for patients with advanced SCCHN and good performance status. prelimi nary response and survival data are encouraging and suggest that further st udy is indicated. The recommended phase II dose of paclitaxel by CI is 10.5 mg/m(2)/d with RT for SCCHN. J Clin Oncol 19:1363-1373. (C) 2001 by Americ an Society of Clinical Oncology.