Phase III trial of irinotecan plus infusional 5-fluorouracil/folinic acid versus irinotecan plus oxaliplatin as first-line treatment of advanced colorectal cancer

Abstract

Purpose To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC). Patients and methods A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80 mg/m 2, 5-fluorouracil 2000 mg/m 2, folinic acid 500 mg/m 2 weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m 2 applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS). Results A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [hazard ratio = 1.14; 95% confidence interval (CI) 0.94–1.37; P = 0.178]. Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm (hazard ratio = 1.08, P = 0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P = 0.001). Most frequent grades 1–4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3–4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P = 0.006) Conclusion mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer.