Optimal Scheme of Postoperative Chemoradiotherapy in Rectal Cancer: Phase III Prospective Randomized Trial

Kim, Young Seok; Kim, Jong Hoon; Choi, Eun Kyung; Ahn, Seung Do; Lee, Sang Wook; Kim, Kyoung Ju; Lee, Je Hwan; Kim, Jin Cheon; You, Chang Sik; Kim, Hee Cheol

Abstract

PURPOSE: To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, patterns of failure, toxicities in early and late radiotherapy groups using a phase III randomized prospective clinical trial.
MATERIALS AND METHODS
From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm I)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU 375 mg/m2/day, leucovorin 20 mg/ m2, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months.
RESULTS
Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were 78.3% and 68.7% in arm I, and 78.4% and 67.5% in arm II. The local recurrence rate was 6.6% and 6.4% ( p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms (23.8% and 29.5%, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in 63.0% and 58.2% of the respective arms ( p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only 1.3% and 2.6% of patients in each respective arm.
CONCLUSION
There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.