PROSPECTIVE PHASE-I EVALUATION OF RADIATION-THERAPY, 5-FLUOROURACIL, AND LEVAMISOLE IN LOCALLY ADVANCED GASTROINTESTINAL CANCER

Purpose: A recent clinical trial in patients with resected node-positi ve colon cancer demonstrated a clear survival advantage for patients t reated with adjuvant 5-fluorouracil and levamisole. This finding led t o interest in development of a Phase III trial comparing 5-fluorouraci l and levamisole with 5-fluorouracil, levamisole, and radiation therap y in colon cancer patients at high risk for local recurrence. A prospe ctive evaluation of 5-fluorouracil, levamisole, and radiation therapy was undertaken with the goal of establishing a satisfactorily tolerate d regimen. Methods and Materials: Fifteen patients were studied who ha d locally advanced or locally recurrent upper abdominal gastrointestin al cancer (11 patients) or large bowel cancer confined to the pelvis ( 4 patients). The tumor and regional lymph nodes received 45 Gy in 25 f ractions. Patients with pelvic tumors subsequently were treated with a radiation boost of 5.4-9 Gy in 3-5 fractions. Systemic therapy consis ted of 5-fluorouracil, 450 mg/m(2), given intravenously for 3 consecut ive days during the first and last weeks of radiation therapy. Levamis ole, 50 mg, given orally 3 times daily was used for 3 consecutive days concurrent with initiation of radiation therapy and 5-fluorouracil, a t the beginning of the third week of radiation therapy, and concurrent with the final 3-day course of 5-fluorouracil. Results: Therapy was g enerally well tolerated. in two patients, equal to or greater than gra de 3 nonhematologic toxicity developed and consisted of transient smal l bowel obstruction in one and severe nausea and vomiting related to l evamisole administration in another. One patient experienced grade 3 h ematologic toxicity with a leukocyte count nadir of 1,600 cells/mu L. Conclusions: These results are similar to the toxicity profile reporte d elsewhere for radiation therapy and 5-fluorouracil. The addition of levamisole to radiation therapy and 5-fluorouracil does not appear to increase toxicity significantly.