{"entity":{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","aka":[],"tldr":"FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.","summary":"Infusional 5-fluorouracil with leucovorin plus oxaliplatin every 2 weeks. MOSAIC (2004) established it as adjuvant therapy for stage III colon cancer; IDEA (2018) showed 3 months suffices for low-risk stage III with CAPOX. In mCRC it pairs with bevacizumab, cetuximab/panitumumab, encorafenib + cetuximab (BREAKWATER), or tucatinib + trastuzumab (MOUNTAINEER-03). Cumulative oxaliplatin neuropathy is the limiting toxicity.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/FOLFOX","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/FOLFOX"},{"label":"Oettle et al., CONKO-003 (JCO 2014)","url":"https://doi.org/10.1200/JCO.2013.53.6995"},{"label":"Gill et al., PANCREOX (JCO 2016)","url":"https://doi.org/10.1200/JCO.2016.68.5776"}],"tags":[],"related":["folfiri","capox","folfirinox"],"cancers":["colorectal","gastric","pancreatic","pancreatic-acinar-cell-carcinoma","appendiceal-adenocarcinoma","goblet-cell-adenocarcinoma","localised-small-bowel-adenocarcinoma","advanced-small-bowel-adenocarcinoma","gallbladder","cholangiocarcinoma","metastatic-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["breakwater","paradigm","atomic","mountaineer","nct07221357","nct07702032","nct05482893","nct07659795","nct04068610","nct03526835","nct06324357","nct02671435","nct07498725","abc-06","sevilla","combomatch-binimetinib-folfox","conko-003","sequoia","alliance-a021501","primus-001","mosaic","idea-collaboration","scot","foxtrot","eortc-40983","prospect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Gallbladder cancer: ABC-06, the UK phase 3 that made FOLFOX the second-line standard for biliary tract cancer (overall survival 6.2 versus 5.3 months, hazard ratio 0.69), enrolled gallbladder and ampullary carcinoma alongside cholangiocarcinoma. FOLFOX is the comparator in the UK-French SEVILLA trial of ivonescimab and the backbone of the ComboMATCH binimetinib trial.","Pancreatic cancer: oxaliplatin with fluorouracil and folinic acid is a second-line option after gemcitabine on CONKO-003 (OFF schedule: overall survival 5.9 against 3.3 months), but PANCREOX found modified FOLFOX6 worse than fluorouracil and leucovorin alone (6.1 against 9.9 months); FOLFOX was the control arm of SEQUOIA (6.3 months) and the post-operative regimen in Alliance A021501."],"code":"mFOLFOX6","modality":"Cytotoxic regimen","mechanism":"5-FU inhibits thymidylate synthase (potentiated by leucovorin); oxaliplatin forms platinum-DNA adducts.","approvals":[{"region":"US","year":2004,"indication":"Adjuvant stage III colon cancer (oxaliplatin, MOSAIC)"}],"mechanismSteps":["Oxaliplatin crosslinks DNA so it cannot be copied","5-FU blocks the enzyme that makes the building block thymidine","Leucovorin locks 5-FU onto that enzyme for longer","Rapidly dividing cancer cells cannot replicate and die"],"dosing":{"route":"Intravenous","schedule":"Oxaliplatin 85 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":"Stop or reduce oxaliplatin for persistent grade 2 neuropathy; DPD deficiency testing before 5-FU is recommended in Europe","monitoring":"Blood counts, neuropathy, liver function"},"toxicity":[{"event":"Peripheral sensory neuropathy","note":"Cumulative, often persistent; oxaliplatin"},{"event":"Neutropenia"},{"event":"Diarrhoea, mucositis"},{"event":"Cold-induced dysaesthesia","note":"Acute, oxaliplatin"}],"access":[],"regulatoryEvents":[]},"route":"/drugs/folfox/","neighbours":{"drug":[{"id":"capox","kind":"drug","name":"CAPOX (capecitabine, oxaliplatin)","route":"/drugs/capox/"},{"id":"flot","kind":"drug","name":"FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)","route":"/drugs/flot/"},{"id":"folfiri","kind":"drug","name":"FOLFIRI (5-FU, leucovorin, 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