Trial Information

PHASE I TRIAL OF POST-OPERATIVE COMBINED ORAL UFT PLUS LEUCOVORIN AND RADIATION THERAPY FOR RECTAL CANCER

OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of
postoperative fluorouracil-uracil plus leucovorin calcium concurrently with radiotherapy in
patients with colorectal cancer. II. Determine the toxicity of this regimen in these
patients. III. Determine the response of tumors in patients with measurable disease treated
with this regimen.

OUTLINE: This is a dose-escalation study of fluorouracil-uracil (UFT). Beginning within 10
weeks after definitive surgery, patients receive oral UFT and oral leucovorin calcium (CF) 3
times a day on days 1-28. Treatment continues every 5 weeks for 2 courses in the absence of
disease progression or unacceptable toxicity. Beginning on day 1 of the second course,
patients undergo radiotherapy to the tumor bed and involved lymph nodes 5 days a week for 5
weeks, followed by boost radiotherapy to the primary tumor bed for 5-16 days. Patients
receive 3 additional courses of UFT plus CF beginning 4 weeks after completion of
radiotherapy or after recovery from the toxic effects of UFT, whichever occurs later.
Patients who have measurable disease with ongoing response after the fifth course receive
additional courses of UFT and CF. Cohorts of 3-6 patients receive escalating doses of UFT
during the second course until the maximum tolerated dose (MTD) is determined. The MTD is
defined as highest dose at which the minority of patients experience dose-limiting toxicity.
Patients are followed every 3 months for 1 year and then at the discretion of the
investigator.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.