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

2010; Elsevier BV; Volume: 47; Issue: 2 Linguagem: Inglês

10.1016/j.ejca.2010.09.022

1879-0852

Ludwig Fischer von Weikersthal, Andreas Schalhorn, Martina Stauch, D. Quietzsch, P. Maubach, Helmut Lambertz, Daniel Oruzio, Rudolf Schlag, K. Weigang-Köhler, U. Vehling-Kaiser, Manfred Schulze, J. Truckenbrodt, Mariele Goebeler, J. Mittermüller, Daniel Bosse, Borika Szukics, Marc Grundeis, Thomas Zwingers, Clemens Gießen, Volker Heinemann,

Gastric Cancer Management and Outcomes

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/m2, 5-fluorouracil 2000 mg/m2, folinic acid 500 mg/m2 weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m2 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.