Postoperative adjuvant chemoradiotherapy for rectal cancer: Analysis of acute and chronic toxicity

Aims and background: The aim of the study was to evaluate acute and chronic toxicity of combined postoperative standard radiation therapy to the pelvis and 5-fluorouracil plus levamisole in resectable rectal cancer. Methods: Between July 1990 and September 1993, 58 patients with histologically confirmed adenocarcinoma of the rectum entered the prospective study. The schedule consisted of 5-fluorouracil, 450 mg/m² i.v. for 5 days, and from day 28 5-fluorouracil, 450 mg/m² i.v. weekly for 24 weeks, plus levamisole given orally at the dose of 150 mg every day for 3 days every 2 weeks for 6 months; radiotherapy (180 cGy/day) 5 days a week for a total dose of 45 Gy was administered from day 28. Results: After the first cycle of chemotherapy (before radiotherapy), overall toxicity was mild. During chemoradiotherapy dose-limiting toxicity was grade 3 diarrhea and proctitis, for which the combined treatment was interrupted for more than 7 cumulative days in 28 patients. During the 24 weeks of weekly 5-fluorouracil (after radiotherapy), no severe toxicity was reported. Three-year survival and progression-free survival were 65% and 50-55%, respectively. Conclusions: Although adjuvant chemoradiotherapy is usually feasible, in our study toxicity was severe in a substantial proportion of patients, probably due to the schedule applied. We are evaluating the feasibility and toxicity of a combined treatment which includes 5-fluorouracil in continuous chronomodulated infusion during radiotherapy.