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Chemotherapy of FOLFIRI causes direct cytotoxic damage to tumor cells.<\/jats:p>\n <\/jats:sec>\n \n Objectives:<\/jats:title>\n \n We evaluated the efficacy and safety of regorafenib plus FOLFIRI with\n uridine diphosphate glucuronosyltransferase 1A1<\/jats:italic>\n (\n UGT1A1<\/jats:italic>\n ) genotyping-guided irinotecan dose escalation in patients with metastatic colorectal cancer (mCRC) who had received second- or third-line systemic therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Design:<\/jats:title>\n A total of 153 patients were randomized (at a ratio of 2:1) to receive either regorafenib plus FOLFIRI (experimental group, 102 patients) or regorafenib alone (control group, 51 patients).<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Both groups received regorafenib (120\u2009mg daily) for 21 consecutive days in 28-day cycles. In addition, the experimental group received FOLFIRI with\n UGT1A1<\/jats:italic>\n genotyping-guided irinotecan dose escalation. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), disease control rate (DCR), and adverse events.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The final cohort included 116 patients. The experimental group exhibited significant improvement in PFS (\n p<\/jats:italic>\n \u2009=\u20090.016) but marginally significant improvements in DCR (\n p<\/jats:italic>\n \u2009=\u20090.055). Specifically, PFS improved significantly for experimental group patients carrying wild-type\n rat sarcoma virus<\/jats:italic>\n (\n RAS; p<\/jats:italic>\n \u2009=\u20090.003) and those carrying left-sided colon tumors (\n p<\/jats:italic>\n \u2009=\u20090.015). A trend toward improved OS was noted in experimental group patients carrying wild-type\n RAS<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009=\u20090.096). No significant between-group difference was observed in the incidence of severe adverse events (all\n p<\/jats:italic>\n \u2009>\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Our findings suggest that regorafenib plus FOLFIRI significantly improved PFS in patients with mCRC and offers a safety profile similar to that of regorafenib alone. This regimen may be particularly beneficial for patients with mCRC carrying wild-type\n RAS<\/jats:italic>\n and those carrying left-sided tumors. However, larger phase III randomized controlled trials are necessary to confirm the efficacy and safety of this combination therapy before adoption into standard practice.\n <\/jats:p>\n <\/jats:sec>\n \n Trial registration:<\/jats:title>\n \n ClinicalTrials.gov registry: NCT03880877 (\n https:\/\/clinicaltrials.gov\/search?cond=NCT03880877<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/17588359251371489","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:28:10Z","timestamp":1761204490000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of regorafenib plus FOLFIRI with\n UGT1A1<\/i>\n genotyping-guided irinotecan dose escalation against metastatic colorectal cancer: a multicenter, phase II, open-label, two-arm randomized controlled tria"],"prefix":"10.1177","volume":"17","author":[{"given":"Ching-Wen","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao-Wei","family":"Ker","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tainan Municipal Hospital (Managed by Show Chwan Care Corporation), Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung-Kun","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chih","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, 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