A Phase I Study of Concomitant Chemoradiotherapy With 776C85, 5-FU and Hydroxyurea for Patients With Poor Prognosis Oral Cancer

OBJECTIVES: I. Assess the feasibility of the administration of ethynyluracil concurrently with fluorouracil and radiotherapy in patients with advanced oral cancer. II. Determine the maximum tolerated dose (MTD) and dose-limiting toxicities of this regimen in this patient population.

OUTLINE: This is a dose escalation study of fluorouracil and hydroxyurea. Patients receive oral ethynyluracil every 12 hours on days 1-7 and oral fluorouracil every 12 hours on days 2-6. Radiotherapy to the head and neck is administered twice daily on days 2-6. Treatment continues for 5-7 courses in the absence of unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities. Once the MTD of fluorouracil is determined, hydroxyurea is added to the treatment regimen. Patients receive fluorouracil and ethynyluracil as per the treatment schedule outlined above. Patients also receive oral hydroxyurea every 12 hours for 11 doses on days 1-6. Radiotherapy is administered as above. Cohorts of 3-6 patients receive escalating doses of hydroxyurea until the MTD is determined. Once the MTD of fluorouracil and hydroxyurea are determined, an additional 10 patients receive Phase II doses of ethynyluracil, fluorouracil and hydroxyurea as per the treatment schedule outlined above. Treatment continues in the absence of unacceptable toxicity. Patients are followed at 4-6 weeks, then every 6 months until death.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study over 2 years.