# Leucovorin (folinic acid)

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

## TL;DR

Leucovorin is not a cancer drug in itself: it rescues normal tissue after high-dose methotrexate and, given with fluorouracil, makes that chemotherapy work better, which is why it appears in FOLFOX, FOLFIRI and FOLFIRINOX.

## Summary

Leucovorin (folinic acid, calcium folinate) is a form of folate that cells can use without the enzyme methotrexate blocks. Given after high-dose methotrexate it lets normal bone marrow and gut recover while the drug has already acted on the tumour; given with fluorouracil it increases the drug's binding to its target enzyme thymidylate synthase, an effect that underlies every fluorouracil-based bowel, stomach and pancreatic cancer regimen. Levoleucovorin is the active isomer alone at half the dose. It is a generic medicine on the WHO essential medicines list.

## Fields

- Kind: Treatment
- Status: established
- Last checked: 2026-09-08
- Also known as: Leucovorin Calcium; Folinic acid; Calcium folinate; Levoleucovorin (Fusilev, Khapzory)
- Tags: gap-fill; generic
- Brand: Wellcovorin / generic
- Modality: Reduced folate (rescue agent and chemotherapy modulator)
- Mechanism: A reduced folate that bypasses dihydrofolate reductase, rescuing normal cells from methotrexate, and that stabilises the fluorouracil-thymidylate synthase complex to make fluorouracil more effective.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Folinic_acid
- Label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=leucovorin%20calcium

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)](https://onco.cc/cancers/all-paediatric-high-risk/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Generic sterile injectables (the 2023 platinum shortage)](https://onco.cc/technologies/sterile-injectable-generics-manufacturing/)
- targets: [Dihydrofolate reductase (DHFR)](https://onco.cc/targets/dhfr/), [Thymidylate synthase (TYMS)](https://onco.cc/targets/tyms/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [FOLFOXIRI (5-FU, leucovorin, oxaliplatin, irinotecan)](https://onco.cc/drugs/folfoxiri/), [Methotrexate](https://onco.cc/drugs/methotrexate/)
- trials: [5-Fluorouracil/Leucovorin (5FU/LV) in Combination With Regorafenib in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct06887218/), [A Clinical Study of Liposomal Irinotecan for Second-Line Therapy in Metastatic Colorectal Cancer](https://onco.cc/trials/nct07585279/), [A Phase 2 Study of SSGJ-707 in Metastatic Colorectal Cancer Patients](https://onco.cc/trials/nct06493760/), [A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer](https://onco.cc/trials/nct05846867/), [A Study of AK104 With Chemotherapy as First-line Treatment in Patients With Advanced Pancreatic Cancer](https://onco.cc/trials/nct05859750/), [A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy](https://onco.cc/trials/nct06750094/), [A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer](https://onco.cc/trials/nct06662786/), [A Study of MRG007 Combination Therapy for Advanced Colorectal Cancer](https://onco.cc/trials/nct07737600/), [A Study of SHR-1826 for Injection in Combination With Other Antitumor Therapies in Subjects With Solid Tumors](https://onco.cc/trials/nct06703177/), [A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer](https://onco.cc/trials/nct03505320/), [A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer](https://onco.cc/trials/nct06901531/), [A Study on the Efficacy and Safety of Irinotecan Liposome (II), 5-FU/LV in Combination With Bevacizumab for the Treatment of Advanced Colorectal Cancer](https://onco.cc/trials/nct07123441/), [ABC-06](https://onco.cc/trials/abc-06/), [Abemaciclib Combined With FOLFOX/FOLFIRI Regimen in Patients With Advanced Colorectal Liver Metastases Cancer](https://onco.cc/trials/nct07441369/), [Adebelimab Combined With Irinotecan Liposomal Injection, Oxaliplatin, Fluorouracil and Calcium Folinate Are Used in the First-line Treatment of Pancreatic Cance](https://onco.cc/trials/nct06531278/), [Anlotinib Plus Nab-Paclitaxels and S-1 for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment](https://onco.cc/trials/nct06662877/), [AVF2107g](https://onco.cc/trials/avf2107g/), [BALLAD](https://onco.cc/trials/ballad/), [BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours](https://onco.cc/trials/nct04421820/), [Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil for Advanced Cholangiocarcinoma](https://onco.cc/trials/nct06438822/), [Cediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer](https://onco.cc/trials/nct00399035/), [Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery](https://onco.cc/trials/nct04068103/), [Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct00628810/), [Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations](https://onco.cc/trials/nct02883049/), [Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia](https://onco.cc/trials/nct00557193/), [ComboMATCH: FOLFOX with or without binimetinib in second-line biliary tract cancer with MAPK pathway alterations](https://onco.cc/trials/combomatch-binimetinib-folfox/), [CONKO-003 (OFF)](https://onco.cc/trials/conko-003/), [DCE-MRI for Neoadjuvant Treatment Assessment in Patients With Borderline Resectable Pancreatic Cancer](https://onco.cc/trials/nct07705919/), [EORTC 40983](https://onco.cc/trials/eortc-40983/), [ESOPEC](https://onco.cc/trials/esopec/), [ESPAC-1](https://onco.cc/trials/espac-1/), [ESPAC-3](https://onco.cc/trials/espac-3/), [Evaluation of Irinotecan Liposome (II) Combined With 5-FU, LV, and Bevacizumab for mCRC](https://onco.cc/trials/nct06643793/), [Evaluation of the Preliminary Efficacy and Safety of DR30206 in Combination With Standard Therapy in Patients With Gastrointestinal Cancer](https://onco.cc/trials/nct07056777/), [First in Human Study of AZD9592 in Solid Tumors](https://onco.cc/trials/nct05647122/), [FLOT4-AIO](https://onco.cc/trials/flot4/), [FOLFOX, Botensilimab, and Balstilimab for the Treatment of Localized Rectal Cancer Before Surgery](https://onco.cc/trials/nct06780787/), [FOLFOX8 Versus mFOLFOX6 With Bevacizumab or Cetuximab for First-Line Unresectable Metastatic Colorectal Cancer (Phase II)](https://onco.cc/trials/nct07621497/), [FUDR/Oxaliplatin HAI Plus Irinotecan vs. FOLFOXIRI Chemotherapy in Treating Initially Unresectable CRCLM](https://onco.cc/trials/nct03678428/), [G-CSF in Preventing Neutropenia During First-Line Treatment With Chemotherapy and Bevacizumab in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct00541125/), [High Dose Methotrexate With Leucovorin Rescue With or Without Glucarpidase in Osteosarcoma](https://onco.cc/trials/nct00634322/), [HR070803 in Combination With Oxaliplatin, 5-fluorouracil/LV Versus GX as Adjuvant Therapy for Pancreatic Cancer](https://onco.cc/trials/nct06217042/), [HR070803 in Combination With Oxaliplatin, S-1 Versus NALIRIFOX as Adjuvant Therapy for Pancreatic Cancer](https://onco.cc/trials/nct06383078/), [Hypofractionated Radiotherapy Plus Immunotherapy Versus Conventional Radiotherapy in Locally Recurrent Rectal Cancer](https://onco.cc/trials/nct06928584/), [INT-0116 (Macdonald trial)](https://onco.cc/trials/int-0116/), [Irinotecan Hydrochloride Liposome Injection (II)in Combination With Oxaliplatin, 5-FU/LV Versus AG for First-line Treatment of Metastatic Pancreatic Cancer](https://onco.cc/trials/nct07238283/), [Irinotecan Liposome for Resectable Pancreatic Cancer With or Without Addebelizumab](https://onco.cc/trials/nct06172036/), [Liposomal Irinotecan + Oxaliplatin + Bevacizumab Versus Liposomal Irinotecan + 5-FU/LV](https://onco.cc/trials/nct06782685/), [Liposomal Irinotecan and Leucovorin/5-fluorouracil Plus Bevacizumab in Metastatic Colorectal Cancer](https://onco.cc/trials/nct06184698/), [Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT for Locally Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07797816/), [Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE](https://onco.cc/trials/nct04919226/), [mFOLFOX/mFOLFIRI vs. mFOLFOX in Advanced or Recurrent Biliary Tract Cancer Second-line](https://onco.cc/trials/nct07062536/), [MOSAIC](https://onco.cc/trials/mosaic/), [NALIRICC (AIO)](https://onco.cc/trials/naliricc/), [NAPOLI-1](https://onco.cc/trials/napoli-1/), [NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer](https://onco.cc/trials/nct04005339/), [NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Untreated Metastatic Pancreatic Cancer](https://onco.cc/trials/nct06941857/), [Neoadjuvant/Adjuvant AK104 in Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer](https://onco.cc/trials/nct07412613/), [Netherlands Cancer Institute HIPEC trial](https://onco.cc/trials/netherlands-hipec/), [NIFE (AIO-YMO HEP-0315)](https://onco.cc/trials/nife/), [NIFTY](https://onco.cc/trials/nifty/), [Palliative Chemotherapy in Treating Patients With Advanced Colorectal Cancer](https://onco.cc/trials/nct00002893/), [PANOPTIMOX-PRODIGE 35](https://onco.cc/trials/panoptimox-prodige-35/), [Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma](https://onco.cc/trials/nct07214298/), [Perioperative Treatment in High-risk Resectable Pancreatic Cancer With NALIRIFOX](https://onco.cc/trials/nct06210360/), [PETACC-3](https://onco.cc/trials/petacc-3/), [Phase II Study of Irinotecan Liposomes in First-line Treatment of Metastatic Colorectal Cancer](https://onco.cc/trials/nct06341296/), [Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases,](https://onco.cc/trials/nct07271355/), [PRODIGE 4 / ACCORD 11](https://onco.cc/trials/prodige-4-accord-11/), [PRODIGE 7](https://onco.cc/trials/prodige-7/), [QUASAR](https://onco.cc/trials/quasar/), [Rituximab, Rasburicase, and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma](https://onco.cc/trials/nct00057811/), [Second-line Doublet Chemotherapy (FOLFOX or FOLFIRI) Plus Fruquintinib Versus Doublet Chemotherapy (FOLFOX or FOLFIRI) Plus Bevacizumab in Metastatic Colorectal](https://onco.cc/trials/nct07150403/), [Sequential Anti-Angiogenic Therapy After Immunotherapy in Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07025174/), [Sintilimab Plus NALIRIFOX or Gemcitabine-Cisplatin as First-Line Treatment for Metastatic Biliary Tract Cancer](https://onco.cc/trials/nct07831993/), [Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metast](https://onco.cc/trials/nct07775287/), [Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta](https://onco.cc/trials/nct07621718/), [Study to Assess Adverse Events and Change in Disease Activity in Previously Treated Adult Participants Receiving Intravenous (IV) ABBV-400 With Unrese](https://onco.cc/trials/nct06107413/), [Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal C](https://onco.cc/trials/nct02885753/), [Tegafur-Uracil and Leucovorin or S-1 in Treating Patients With Stage III Colon Cancer That Has Been Completely Removed by Surgery](https://onco.cc/trials/nct00660894/), [Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer](https://onco.cc/trials/nct06958328/), [Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial](https://onco.cc/trials/nct05863195/), [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/), [The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer](https://onco.cc/trials/nct05628038/), [The Sagittarius Trial](https://onco.cc/trials/nct06490536/), [Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer](https://onco.cc/trials/nct04094688/), [Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?](https://onco.cc/trials/nct02022358/)
- key papers: [Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study (QUASAR)](https://onco.cc/key-papers/paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007/), [Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7)](https://onco.cc/key-papers/paper-quenet-prodige-7-hipec-peritoneal-colorectal-lancet-oncol-2021/), [Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma](https://onco.cc/key-papers/paper-moertel-levamisole-fluorouracil-adjuvant-colon-nejm-1990/), [Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer (MOSAIC)](https://onco.cc/key-papers/paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004/), [Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer](https://onco.cc/key-papers/paper-verwaal-cytoreduction-hipec-peritoneal-colorectal-jco-2003/)

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