A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer

Background: Studies indicate that adjuvant 5-fluorouracil (5-FU) with folinic acid (FA) in colorectal cancer patients with completely resectable liver-limited metastases (LMCRC) offers clinical benefit over surgery alone. This phase III trial compared FOLFIRI with simplified 5-FU/FA in this setting. Patients and methods: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m 2 infused over 2 h, followed by 5-FU as a 400 mg/m 2 i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m 2 over 46 h (LV5FUs) with or without irinotecan: 180 mg/m 2 infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety. Results: Treated patients ( n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47% versus 30%) with neutropenia being most common (23% versus 7%). Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.