Seven-week continuous-infusion paclitaxel concurrent with radiation therapy for locally advanced non-small cell lung and head and neck cancers

The goal of these National Cancer Institute-sponsored phase I trials is to determine the feasibility, toxicity, and pharmacokinetics of continuous- infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel combined with standard, curative-intent thoracic radiation therapy (XRT) for previously untreated, locally advanced non-small cell lung cancer and squamous cell cancer of the head and neck (HNSCC). Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell lung cancer ineligible for potentially curative surgical resection or locally advanced HNSCC with an expected 5-year survival rate of less than 25%, as well as a good performance status, adequate hematologic, hepatic, and renal function, and no distant metastases. Non-small cell lung cancer patients receive a total tumor dose of 64.8 Gy megavoltage XRT in 7 weeks at 1.8 Gy once daily, 5 d/wk. Patients with HNSCC receive 70 Gy megavoltage XRT in 7 weeks at 2 Gy once daily, 5 d/wk. Paclitaxel is delivered by continuous intravenous infusion starting 48 hours before XRT and continuing for its duration. The close of paclitaxel is escalated in cohorts of three patients in a standard phase I design. To date, 49 patients have been entered on both studies and 43 are evaluable for toxicity. Paclitaxel dose is currently at the 17 mg/m²/d dose level, with no dose-limiting toxicity thus far. Clinical outcomes suggest significant activity for this combination. This therapy is feasible and has been well- tolerated through current close levels. Dose escalation is ongoing.