Phase I study of UFT plus leucovorin with radiotherapy in patients with inextirpable non-rectal gastrointestinal cancer.

BACKGROUND AND PURPOSE: Chemoradiotherapy is increasingly used in the primary management of patients with loco-regionally advanced gastrointestinal (GI) cancer. Oral chemotherapy with uracil and tegafur (UFT) plus leucovorin (LV) may represent a convenient way of delivering protracted infusion of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with radiation and determine the maximum-tolerated dose (MTD) and a recommended dose for further testing. PATIENTS AND METHODS: Patients with inextirpable GI cancer received escalating doses of UFT (starting at 300 mg/m(2)/d with 50 mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). UFT and LV were given 5 days per week concurrently with radiation to 50 Gy (2 Gy/fraction). RESULTS: Twenty-five patients were treated, and 22 received the planned treatment. Three patients were withdrawn from treatment, two due to disease-progression and one due to toxicity. The MTD of UFT with radiation was 400 mg/m(2)/d with 90 mg/d of LV. Diarrhoea was the main dose limiting toxicity (DLT). Since some toxicity (3/12 DLTs) was seen in the expanded cohort at the level below, but none (0/9 DLT) at the starting level, the recommended dose chosen for further testing is 300-350 mg/m(2)/d depending upon the size of the target volume. CONCLUSION: Concomitant chemoradiation with oral UFT plus LV is feasible and well tolerated and should be further investigated since tumour responses were frequently seen.