PURPOSE: Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients.

PATIENTS AND METHODS: Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable.

Patients who were assigned to receive chemotherapy without radiation therapy received weekly doses of fluorouracil 450 mg/m2 intravenously, beginning 28 days after the first dose of chemotherapy, until therapy had been given for a total of 1 year.

Patients assigned to receive chemoRT began radiation therapy 28 days after the first fluorouracil dose. A total dose of 45 Gy in 25 fractions was given to fields designed to encompass the preoperative tumor volume and regional lymph nodes, including the adjacent para-aortic or pelvic lymph nodes. An additional three fractions of 1.8 Gy each were given to the preoperative tumor volume if all small bowel could be excluded from this boost field. The protocol required that two-thirds of the liver receive less than 30 Gy, that at least two-thirds of one kidney receive less than 20 Gy (as assessed by excretory urography done at simulation or CT scan), and that the maximal dose to the spinal cord be less than 50 Gy. Systemic treatment during radiation therapy consisted of fluorouracil 450 mg/m2 given intravenously on the days of the first, second, and third radiation fractions, and again on the days of the 23rd, 24th, and 25th radiation fractions. During radiation therapy, levamisole 50 mg by mouth was given three times daily for 3 days approximately every 2 weeks, beginning with the day of the first, 11th, and 23rd radiation fractions. Weekly treatment with fluorouracil was initiated 28 days after completion of radiation therapy according to the same schedule and dose as the weekly treatment administered to the patients assigned to receive chemotherapy alone. As with those patients, treatment continued until therapy had been given for a total of 1 year.

RESULTS: Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P > .50); 5-year disease-free survival was 51% for both groups (P > .50). Toxicity ( grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P = .04). Leukopenia ( grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P = .02). No significant difference in nonhematologic toxicity ( grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P = .26).

CONCLUSION: Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences.