A pilot study of concomitant protracted venous infusion 5-fluorouracil and hyperfractionated radiotherapy in rectal...

It has recently been shown that postoperative radiotherapy combined with 5-fluorouracil (5FU) resulted in an increase of survival and local control in patients with rectal cancer. However, hematological and intestinal toxicity were also increased. Experimental and clinical studies showed an increased radiation effect with an acceptable toxicity by delivering 5FU via a continuous intravenous infusion. From July 1988, 38 patients radically operated on for stages B2-C rectal cancer were irradiated in our hospital with 3 fractions per day of 100 cGY to a total dose of 5,600 cGY. Of these 38 patients, 13 underwent postoperative radiotherapy alone, and 25 received postoperative radiotherapy combined with concomitant protracted infusion of 5FU at doses of 250 and 300 mg/m2 per day. In addition, 14 patients with inoperable, locally advanced tumors or postoperative recurrences, were treated with the same combination schedule of 5FU and radiotherapy to a total radiation dose of 6,500 cGy. After a median follow-up of 43 months, the actuarial 3-year overall and disease-free survival rates in the postoperative group of patients were 68% and 68%, respectively, in the combined modality group, as compared to 51% and 36%, respectively, in the radiation alone group. Patients with inoperable tumors exhibited 3-year overall and disease-free survival rates of 24% and 32%, respectively. The main toxicity was rectal tenesmus, diarrhea, dysuria, and, less frequently, leukopenia. These symptoms were responsible for a treatment delay of more than 5 days in 2 of 6 and in 7 of 33 patients who received 5FU doses of 300 and 250 mg/m2 per day, respectively, as compared to 2 of 13 patients treated with radiotherapy alone.