Trial Information

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.