A Phase I Study of Concomitant Chemoradiotherapy With Gemcitabine, Paclitaxel, and 5-FU for Patients With Advanced and/or Recurrent Cancer of the Head and Neck

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine when administered with paclitaxel and fluorouracil with concurrent hyperfractionated radiotherapy in patients with advanced and/or recurrent head and neck cancer. II. Determine the MTD and DLT of gemcitabine as a single agent with radiotherapy in these patients. III. Determine the efficacy of concurrent chemoradiotherapy in terms of time to progression, pattern of failure, and overall survival in patients with measurable disease. IV. Determine gemcitabine and fluorouracil pharmacokinetics in these patients.

OUTLINE: This is a dose escalation study of gemcitabine, conducted in two phases. Phase A: Patients receive fluorouracil IV continuously on days 1-5, paclitaxel IV over 1 hour on day 2, and radiotherapy administered twice daily on days 1-5. This regimen is repeated every 2 weeks for 2 courses, then gemcitabine IV over 30 minutes is added on day 2 after paclitaxel. This regimen is administered every 2 weeks for 3 courses. Patients with responsive disease may continue chemotherapy (without radiotherapy) for 2 courses beyond maximum response. Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity. Phase B: After the MTD of gemcitabine is determined in phase A, further dose escalation of gemcitabine may be performed with concurrent radiotherapy (without fluorouracil or paclitaxel). The MTD is determined as in phase A. Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study within approximately 2 years.