# FOLFOX (5-FU, leucovorin, oxaliplatin)

Source: https://onco.cc/drugs/folfox/  
OnCo record `folfox` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: standard-of-care
- Last checked: 2026-09-07
- Code: mFOLFOX6
- Modality: Cytotoxic regimen
- Mechanism: 5-FU inhibits thymidylate synthase (potentiated by leucovorin); oxaliplatin forms platinum-DNA adducts.
- Approvals: US 2004: Adjuvant stage III colon cancer (oxaliplatin, MOSAIC)
- Dosing: Intravenous; 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

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/FOLFOX
- Wikipedia: https://en.wikipedia.org/wiki/FOLFOX
- Oettle et al., CONKO-003 (JCO 2014): https://doi.org/10.1200/JCO.2013.53.6995
- Gill et al., PANCREOX (JCO 2016): https://doi.org/10.1200/JCO.2016.68.5776

## Connected records

- drugs: [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)](https://onco.cc/drugs/flot/), [FOLFIRI (5-FU, leucovorin, irinotecan)](https://onco.cc/drugs/folfiri/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/)
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Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junct](https://onco.cc/trials/nct05482893/), [SPOTLIGHT & GLOW](https://onco.cc/trials/spotlight-glow/), [Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab fo](https://onco.cc/trials/nct06106308/), [Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorecta](https://onco.cc/trials/nct07702032/), [Study to Evaluate the Use of Capecitabine in Monotherapy and in Combination With Oxaliplatin in Elderly Patients as Adjuvant Chemotherapy for Locally Advanced C](https://onco.cc/trials/nct06888843/), [Testing Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers](https://onco.cc/trials/nct07437287/), [Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage](https://onco.cc/trials/nct05610163/), [Testing the Addition of Atezolizumab to Combination Chemotherapy or Atezolizumab Alone for Metastatic Colon or Rectal Cancer, the COMMIT Study](https://onco.cc/trials/nct02997228/), [The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer](https://onco.cc/trials/nct05628038/), [The Combination of Immunotherapy and Neoadjuvant Short-course Radiotherapy in Early Rectal Cancer](https://onco.cc/trials/nct05555888/), [The Efficacy and Safety of Short-course Radiation Combined With Adebrelimab and CAPEOX Neo-adjuvant Therapy for Organ-retention in Patients With MSS/pMMR Ultra](https://onco.cc/trials/nct06266832/), [The Phase 1b/IIa, Open-label, Dose Escalation and Dose Expansion to Evaluate Safety, Tolerability, and Preliminary Efficacy of the Combination of HCB101, Cetuxi](https://onco.cc/trials/nct07204574/), [The Sagittarius Trial](https://onco.cc/trials/nct06490536/), [TOSCA](https://onco.cc/trials/tosca/), [Total Neoadjuvant mFOLFOX6 Plus Suvemcitug and Enlonstobart With Selective Omission of Pelvic Radiotherapy for High-Risk Mid-Rectal Locally Advanced Rectal Canc](https://onco.cc/trials/nct07810114/), [Total Neoadjuvant Therapy in Rectal Cancer](https://onco.cc/trials/nct06162650/), [Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer](https://onco.cc/trials/nct07662031/), [TRIBE2](https://onco.cc/trials/tribe2/), [Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer](https://onco.cc/trials/nct04094688/), [Zolbetuximab With mFOLFOX6 or CAPOX in Claudin 18.2 Overexpressed Advanced or Metastatic Biliary Tract Cancers](https://onco.cc/trials/nct07723534/)
- pairings: [Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC](https://onco.cc/pairings/anti-egfr-left-sided/)
- ideas: [ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-crc/), [Find peritoneal spread while it is still small, and run complete cytoreduction through networks rather than adding heated chemotherapy](https://onco.cc/ideas/idea-crc-peritoneal-disease-found-early-and-treated-in-networks/), [Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint](https://onco.cc/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/), [Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps](https://onco.cc/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/)
- terms: [Living with FOLFOX, CAPOX, FOLFIRI and the EGFR antibodies](https://onco.cc/terms/chemotherapy-side-effects-colorectal/), [Pancreatic cancer: the failed and stopped programmes and why](https://onco.cc/terms/pancreatic-failed-programmes/)
- people: [Matt Seymour](https://onco.cc/people/matt-seymour/), [Paulo Hoff](https://onco.cc/people/hoff-paulo/), [Tim Maughan](https://onco.cc/people/tim-maughan/)
- key papers: [Duration of adjuvant chemotherapy for stage III colon cancer (the IDEA collaboration)](https://onco.cc/key-papers/paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018/), [Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)](https://onco.cc/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/), [Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-localised-colon-cancer-guideline-ann-oncol-2020/), [Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23)](https://onco.cc/key-papers/paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021/), [Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA)](https://onco.cc/key-papers/paper-garcia-aguilar-opra-organ-preservation-jco-2022/), [Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer (MOSAIC)](https://onco.cc/key-papers/paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004/), [Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)](https://onco.cc/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/), [Preoperative chemotherapy for operable colon cancer: mature results of an international randomized controlled trial (FOxTROT)](https://onco.cc/key-papers/paper-foxtrot-preoperative-chemotherapy-colon-jco-2023/), [Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial](https://onco.cc/key-papers/paper-abc-06-folfox-second-line-lancet-oncol-2021/), [Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)](https://onco.cc/key-papers/paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021/), [The Chicago Consensus on peritoneal surface malignancies: management of appendiceal neoplasms](https://onco.cc/key-papers/paper-chicago-consensus-appendiceal-neoplasms-cancer-2020/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/)

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JSON: https://onco.cc/api/v1/entities/folfox.json