Adjuvant Chemotherapy of Locally Advanced Colon Cancer: Final Results of a Randomized Trial Comparing 5-Fluorouracil and Folinic Acid with Folfiri

Background: There is still the need to optimize adjuvant treatment of colon cancer (CC). Standard adjuvant chemotherapy using 5-fluorouracil (FU) and folinic acid (FA) was compared with a combination including irinotecan (Folfiri). The aim of the present report was to analyze overall survival (OS) after long-term follow-up, to summarize final recurrence rates and toxicity data, and to identify possible clinical and pathological factors associated with prognosis. Methods: Patients (CC stage IIb and III) were randomized to a 6-month treatment with FUFA or Folfiri. The trial was closed after 275 of 588 planned patients, 269 of which were included in the intention-to-treat analysis. Results: 133 and 136 patients received FUFA and Folfiri, respectively. Adjuvant therapy was not completed for 16 FUFA (12.0%) and 44 Folfiri (32.4%) patients. Toxicities grade III and IV were observed in 17 (12.8%) patients treated with FUFA and in 50 (36.8%) patients treated with Folfiri. Recurrences occurred in 46 of 133 (34.6%) and in 47 of 136 (34.6%) patients who received FUFA and Folfiri, respectively. 5-year OS rates were 69.9% (95% confidence interval (CI): 61.2-77.1) for FUFA and 72.7% (95% CI: 63.9-79.8) for Folfiri. OS was associated with tumor grading (1 & 2 vs. 3), tumor sub-stage (II vs. IIIa vs. IIIb vs. IIIc), and tumor location (left vs. right colon). Conclusion: Folfiri cannot be generally recommended for adjuvant chemotherapy of CC. Besides tumor grading and sub-staging, prognosis of CC may depend on tumor location. Left-sided tumors had a significantly better prognosis irrespective of treatment.