FOLFIRI (folinic acid, fluorouracil, and irinotecan) increases not efficacy but toxicity compared with single-agent irinotecan as a second-line treatment in metastatic colorectal cancer patients: a randomized clinical trial

1. Mo, S, Cai, X, Zhou, Z, et al. Nomograms for predicting specific distant metastatic sites and overall survival of colorectal cancer patients: a large population-based real-world study. Clin Transl Med 2020; 10: 169–181.
Google Scholar | Crossref | Medline2. Zhang, J, Yan, S, Liu, X, et al. Gender-related prognostic value and genomic pattern of intra-tumor heterogeneity in colorectal cancer. Carcinogenesis 2017; 38: 837–846.
Google Scholar | Crossref | Medline3. Mo, S, Zhou, Z, Dai, W, et al. Development and external validation of a predictive scoring system associated with metastasis of T1-2 colorectal tumors to lymph nodes. Clin Transl Med 2020; 10: 275–287.
Google Scholar | Crossref | Medline4. Latest global cancer data: cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020 . International Agency for Research on Cancer, World Health Organization, https://www.iarc.who.int/wp-content/uploads/2020/12/pr292_E.pdf
Google Scholar5. Siegel, RL, Miller, KD, Fedewa, SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67: 177–193.
Google Scholar | Crossref | Medline6. Aparicio, J, Esposito, F, Serrano, S, et al. Metastatic colorectal cancer. First line therapy for unresectable disease. J Clin Med 2020; 9: E3889.
Google Scholar | Crossref | Medline7. Gustavsson, B, Carlsson, G, Machover, D, et al. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer 2015; 14: 1–10.
Google Scholar | Crossref | Medline | ISI8. Grothey, A, Sargent, D, Goldberg, RM, et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 2004; 22: 1209–1214.
Google Scholar | Crossref | Medline | ISI9. Xu, RH, Muro, K, Morita, S, et al. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol 2018; 19: 660–671.
Google Scholar | Medline10. Xu, J, Kim, TW, Shen, L, et al. Results of a randomized, double-blind, placebo-controlled, phase III trial of trifluridine/tipiracil (TAS-102) monotherapy in Asian patients with previously treated metastatic colorectal cancer: the TERRA study. J Clin Oncol 2018; 36: 350–358.
Google Scholar | Crossref | Medline11. Li, J, Qin, S, Xu, RH, et al. Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA 2018; 319: 2486–2496.
Google Scholar | Crossref | Medline12. Li, J, Qin, S, Xu, R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619–629.
Google Scholar | Crossref | Medline | ISI13. Tournigand, C, André, T, Achille, E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22: 229–237.
Google Scholar | Crossref | Medline | ISI14. Rothenberg, ML, Oza, AM, Bigelow, RH, et al. Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 2003; 21: 2059–2069.
Google Scholar | Crossref | Medline | ISI15. Cunningham, D, Glimelius, B. A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group. Semin Oncol 1999; 26(1, Suppl. 5): 6–12.
Google Scholar | Medline16. Van Cutsem, E, Blijham, GH. Irinotecan versus infusional 5-fluorouracil: a phase III study in metastatic colorectal cancer following failure on first-line 5-fluorouracil. V302 Study Group. Semin Oncol 1999; 26(1, Suppl. 5): 13–20.
Google Scholar | Medline17. Satoh, T, Ura, T, Yamada, Y, et al. Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci 2011; 102: 1868–1873.
Google Scholar | Crossref | Medline | ISI18. Sobrero, AF, Maurel, J, Fehrenbacher, L, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 2311–2319.
Google Scholar | Crossref | Medline | ISI19. Kim, JH, Park, SJ, Park, MI, et al. FOLFIRI as second-line chemotherapy after failure of FOLFOX4 in advanced colorectal cancer: a Korean single-center experience. Korean J Gastroenterol 2014; 63: 18–24.
Google Scholar | Crossref | Medline20. Van Cutsem, E, Tabernero, J, Lakomy, R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30: 3499–3506.
Google Scholar | Crossref | Medline | ISI21. Seymour, MT, Maughan, TS, Ledermann, JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial [published correction appears in Lancet 2007; 370: 566]. Lancet 2007; 370: 143–152.
Google Scholar | Crossref | Medline | ISI22. Raymond, E, Buquet-Fagot, C, Djelloul, S, et al. Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers. Anticancer Drugs 1997; 8: 876–885.
Google Scholar | Crossref | Medline | ISI23. deBraud, F, Munzone, E, Nolè, F, et al. Synergistic activity of oxaliplatin and 5-fluorouracil in patients with metastatic colorectal cancer with progressive disease while on or after 5-fluorouracil. Am J Clin Oncol 1998; 21: 279–283.
Google Scholar | Crossref | Medline24. de Gramont, A, Figer, M, Seymour, M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18: 2938–2947.
Google Scholar | Crossref | Medline | ISI25. Giacchetti, S, Perpoint, B, Zidani, R, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000; 18: 136–147.
Google Scholar | Crossref | Medline | ISI26. Garufi, C, Brienza, S, Pugliese, P, et al. Overcoming resistance to chronomodulated 5-fluorouracil and folinic acid by the addition of chronomodulated oxaliplatin in advanced colorectal cancer patients. Anticancer Drugs 2000; 11: 495–501.
Google Scholar | Crossref | Medline27. Azrak, RG, Cao, S, Slocum, HK, et al. Therapeutic synergy between irinotecan and 5-fluorouracil against human tumor xenografts. Clin Cancer Res 2004; 10: 1121–1129.
Google Scholar | Crossref | Medline | ISI28. Yamada, T, Furukawa, K, Yokoi, K, et al. Effects of irinotecan and 5-FU combination therapy in gastric cancer – is combination therapy synergic? Gan To Kagaku Ryoho 2010; 37: 2125–2129.
Google Scholar | Medline29. Goldberg, RM, Erlichman, C. Irinotecan plus 5-FU and leucovorin in advanced colorectal cancer: North American trials. Oncology 1998; 12(8, Suppl. 6): 59–63.
Google Scholar | Medline30. Muro, K, Boku, N, Shimada, Y, et al. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol 2010; 11: 853–860.
Google Scholar | Crossref | Medline | ISI31. Yasui, H, Muro, K, Shimada, Y, et al. A phase 3 non-inferiority study of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer: updated results of the FIRIS study. J Cancer Res Clin Oncol 2015; 141: 153–160.
Google Scholar | Crossref | Medline32. Miyamoto, Y, Tsuji, A, Tanioka, H, et al. S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102) [published correction appears in Int J Clin Oncol 2017]. Int J Clin Oncol 2016; 21: 705–712.
Google Scholar | Crossref | Medline33. Takaoka, T, Kimura, T, Shimoyama, R, et al. Panitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer. Cancer Chemother Pharmacol 2016; 78: 397–403.
Google Scholar | Crossref | Medline34. Cassidy, J, Clarke, S, Díaz-Rubio, E, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 2008; 26: 2006–2012.
Google Scholar | Crossref | Medline | ISI35. Saltz, LB, Clarke, S, Díaz-Rubio, E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study [published correction appears in J Clin Oncol 2008; 26: 3110] [published correction appears in J Clin Oncol 2009; 27: 653]. J Clin Oncol 2008; 26: 2013–2019.
Google Scholar | Crossref | Medline | ISI36. Fuchs, CS, Marshall, J, Mitchell, E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol 2007; 25: 4779–4786.
Google Scholar | Crossref | Medline | ISI

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