PURPOSE: To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional5-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.
RCT Entities:
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.
Authors: S Gill; S Berry; J Biagi; C Butts; M Buyse; E Chen; D Jonker; C Mărginean; B Samson; J Stewart; M Thirlwell; R Wong; J A Maroun Journal: Curr Oncol Date: 2011-10 Impact factor: 3.677
Authors: Christopher H Bailey; Gayle Jameson; Chao Sima; Sharon Fleck; Erica White; Daniel D Von Hoff; Glen J Weiss Journal: J Cancer Date: 2011-11-28 Impact factor: 4.207
Authors: D P Modest; I Ricard; V Heinemann; S Hegewisch-Becker; W Schmiegel; R Porschen; S Stintzing; U Graeven; D Arnold; L F von Weikersthal; C Giessen-Jung; A Stahler; H J Schmoll; A Jung; T Kirchner; A Tannapfel; A Reinacher-Schick Journal: Ann Oncol Date: 2016-06-29 Impact factor: 32.976
Authors: Annabel H S Alig; Volker Heinemann; Michael Geissler; Ludwig Fischer von Weikersthal; Thomas Decker; Kathrin Heinrich; Swantje Held; Lena Weiss; Laura E Fischer; Nicolas Moosmann; Arndt Stahler; Ivan Jelas; Annika Kurreck; Jobst C von Einem; Anke C Reinacher-Schick; Andrea Tannapfel; Clemens Giessen-Jung; Sebastian Stintzing; Dominik P Modest Journal: Cancers (Basel) Date: 2022-01-21 Impact factor: 6.639
Authors: C Giessen; L Fischer von Weikersthal; R P Laubender; S Stintzing; D P Modest; A Schalhorn; C Schulz; V Heinemann Journal: Br J Cancer Date: 2013-08-20 Impact factor: 7.640