{"entity":{"id":"folfiri","kind":"drug","name":"FOLFIRI (5-FU, leucovorin, irinotecan)","aka":[],"tldr":"FOLFIRI is the other backbone bowel-cancer chemotherapy, swapping oxaliplatin for irinotecan. Used first or second line and, since 2026, with the BRAF combination.","summary":"FOLFIRI pairs irinotecan, whose active metabolite SN-38 inhibits topoisomerase I, with 5-FU and leucovorin, which inhibit thymidylate synthase, given as a 46-hour infusion every 14 days. It is one of the two backbone chemotherapies for metastatic colorectal cancer, interchangeable with FOLFOX in first-line efficacy (Tournigand 2004) and the standard second-line switch. It is the partner for cetuximab (CRYSTAL, FIRE-3), bevacizumab, aflibercept, ramucirumab and, since 2026, encorafenib plus cetuximab in BRAF V600E disease (BREAKWATER cohort 3, PFS HR 0.44). Diarrhoea, neutropenia and alopecia are the main toxicities, and UGT1A1*28 homozygotes need irinotecan dose reduction. Whether to start with FOLFIRI or FOLFOX is decided by side-effect preference rather than efficacy. For a newcomer, FOLFIRI is bowel cancer chemotherapy with irinotecan instead of oxaliplatin.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/FOLFIRI","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/FOLFIRI"}],"tags":[],"related":["folfox"],"cancers":["colorectal"],"sections":[],"technologies":["cytotoxic-chemotherapy","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["crystal-fire3","breakwater","nct07221357","nct06356311","nct07621718","nct06496048","nct07702032","nct07790510","nct07446322","nct06107413","nct06792695","nct05846867","nct06219941","nct03709680","nct03526835","nct04657068","nct07474727","nct05382442","nct05379595","nct05592626","nct07498725","tribe","tribe2","calgb-80405","velour","raise"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"Cytotoxic regimen","mechanism":"Irinotecan (via SN-38) inhibits topoisomerase I; 5-FU/leucovorin inhibit thymidylate synthase.","approvals":[],"mechanismSteps":["Irinotecan is converted in the body to SN-38","SN-38 traps topoisomerase I on DNA, causing breaks during copying","5-FU with leucovorin starves the cell of thymidine","Dividing cancer cells cannot complete replication"],"dosing":{"route":"Intravenous","schedule":"Irinotecan 180 mg/m² + leucovorin 400 mg/m² day 1, 5-FU 400 mg/m² bolus then 2,400 mg/m² over 46 h, every 14 days","modifications":"Reduce irinotecan for UGT1A1*28/*28; hold for grade 3 diarrhoea","monitoring":"Blood counts; early and late diarrhoea"},"toxicity":[{"event":"Diarrhoea","note":"Early (cholinergic) and late; can be severe"},{"event":"Neutropenia"},{"event":"Alopecia"}],"access":[],"regulatoryEvents":[]},"route":"/drugs/folfiri/","neighbours":{"drug":[{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, 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