Key points
- Fluorouracil (5-FU) is one of the oldest and most widely used chemotherapy drugs; it is used for colorectal, breast, stomach and pancreatic cancer [1].
- It is usually given with leucovorin and other drugs, as a rapid injection followed by a 46-hour pump at home [1].
- After bowel cancer surgery, adding oxaliplatin to this drug made the cancer come back less often [2].
- In a small number of people, an inherited shortage of the DPD enzyme causes very severe side effects; ask about a DPYD gene test before starting [1, 3].
- Important side effects: diarrhoea, mouth sores, low blood counts, hand-foot syndrome and, rarely, chest pain or confusion [1].
What is this drug and how does it work?
For physicians
Fluorouracil is an antimetabolite from the fluoropyrimidine group, described in the FDA label as a nucleoside metabolic inhibitor [1]. In the cell it is converted to three active metabolites: FdUMP, which inhibits thymidylate synthase, FUTP, which is incorporated into RNA, and FdUTP, which is incorporated into DNA; the result is disrupted DNA synthesis and death of rapidly dividing cells [1].
Its half-life after a rapid injection is only 8 to 20 minutes [1], which is why many regimens give it as a continuous infusion. More than 80% of the drug is broken down by the enzyme DPD [1]. Leucovorin (folinic acid) increases the concentration and effect of fluorouracil and is therefore often given with it [4]. Capecitabine (Xeloda) is the oral prodrug of the same drug [4].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Colon and rectal cancer (adenocarcinoma) [1]
- Breast cancer (adenocarcinoma) [1]
- Stomach cancer (adenocarcinoma) [1, 6]
- Oesophageal cancer [7]
- Pancreatic cancer (adenocarcinoma) [1]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Setting |
|---|---|
| Colon and rectal cancer (adenocarcinoma) | Adjuvant treatment after surgery and advanced disease; with leucovorin alone or with oxaliplatin (FOLFOX) or irinotecan [1] |
| Breast cancer (adenocarcinoma) | Part of a cyclophosphamide-based multi-drug regimen [1] |
| Gastric cancer (adenocarcinoma) | Part of a platinum-containing multi-drug regimen, including perioperative FLOT [1, 6] |
| Oesophageal cancer | With cisplatin, as the backbone for combination with immunotherapy in advanced disease (this use is not listed in the fluorouracil FDA label) [7] |
| Pancreatic cancer (adenocarcinoma) | With leucovorin or as part of a multi-drug regimen such as FOLFIRINOX [1] |
| Cancer | Key evidence |
|---|---|
| Colon and rectal cancer (adenocarcinoma) | MOSAIC: 3-year disease-free survival 78.2% with FOLFOX vs 72.9% with fluorouracil/leucovorin [2]; in advanced disease, adding oxaliplatin raised median progression-free survival from 6.2 to 9.0 months [5] |
| Breast cancer (adenocarcinoma) | Approved in the FDA label [1] |
| Gastric cancer (adenocarcinoma) | FLOT4: median overall survival 50 months with FLOT vs 35 months with ECF/ECX (HR 0.77) [6] |
| Oesophageal cancer | KEYNOTE-590: adding pembrolizumab to cisplatin and fluorouracil, median overall survival 12.4 vs 9.8 months (HR 0.73) [7] |
| Pancreatic cancer (adenocarcinoma) | ACCORD 11 (metastatic): median overall survival 11.1 vs 6.8 months with gemcitabine (HR 0.57) [8]; PRODIGE 24 (adjuvant): median overall survival 54.4 vs 35.0 months (HR 0.64) [9] |
HR: hazard ratio; a value below 1 favours the regimen containing the drug or the new combination.
How it is taken and dosing
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Treatment regimens and doses: index5 regimens
Fluorouracil is given only into a vein and is prepared and given at a treatment centre. Depending on the regimen, it is given as a rapid injection (bolus), a continuous infusion or both; long infusions go through a central venous catheter (such as a port) with an infusion pump [1].
- The dose and schedule are set by the type of cancer, the regimen, your body surface area and how well you tolerate it [1].
- A blood count is needed before every cycle; white blood cells are usually lowest 9 to 14 days after the injection [1].
- If a severe side effect happens, your doctor may delay treatment or lower the dose; do not change the schedule yourself and do not miss blood test appointments [1].
- Before starting (boxed warning, revised 10/2025): test for DPYD variants before starting unless treatment is urgent. Avoid use with homozygous or compound heterozygous variants causing complete DPD deficiency (no dose has been shown to be safe); with partial deficiency, individualise the dose by tolerance and treatment goal. A negative test does not exclude all risk [1]. CPIC recommends reducing the starting dose by 50% for an activity score of 1 and by 25 to 50% for 1.5, followed by titration according to tolerance [3].
- Monitoring: CBC before each cycle (neutrophil nadir days 9 to 14); INR or prothrombin time with concomitant warfarin; cardiac and neurological symptoms, especially with continuous infusion [1].
- Withholding and dose reduction: withhold for grade 3 to 4 diarrhoea, grade 2 to 3 hand-foot syndrome, grade 3 to 4 mucositis and grade 4 myelosuppression; after recovery to grade 1, resume at a reduced dose. Withhold for angina, ischaemia or infarction, arrhythmia or heart failure, hyperammonaemic encephalopathy (with ammonia-lowering treatment) and neurological toxicity (acute cerebellar syndrome, confusion, ataxia, visual disturbance); no dose for resuming is recommended for these [1].
- Overdose: uridine triacetate within 96 hours of the end of the infusion [1].
- Administration: bolus through an established IV line; continuous infusion through a central vein with a pump. Do not give in the same IV line as other drugs. Diluted solution or prepared syringe up to 4 hours at room temperature; discard the pharmacy bulk vial 4 hours after puncture [1].
- Kidney and liver: the FDA label gives no specific dose adjustment for renal or hepatic impairment [1].
For physicians
Standard dosing (FDA label, revised 10/2025)
Colorectal, infusional regimen (such as FOLFOX, FOLFIRI or fluorouracil/leucovorin)
Adenocarcinoma of the colon and rectum; with leucovorin alone or with oxaliplatin or irinotecanCycle length: Every 2 weeks
Adenocarcinoma of the colon and rectum; with leucovorin alone or with oxaliplatin or irinotecan [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Each cycle | |||
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 2400 to 3000 mg/m² | Continuous 46-hour IV infusion (central vein, pump) | Starting on day 1 |
Leucovorin and partner drug doses as per their labels [1].
Colorectal, weekly bolus regimen
With leucovorinCycle length: 8-week cycles
With leucovorin [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Each cycle | |||
| Fluorouracil | 500 mg/m² | IV bolus | Days 1, 8, 15, 22, 29 and 36 |
On the weekly schedule, weekly CBC [1].
Breast cancer (cyclophosphamide-based regimen)
Breast adenocarcinoma; part of a multi-drug regimenCycle length: Every 28 days
Breast adenocarcinoma; part of a multi-drug regimen [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Each cycle | |||
| Fluorouracil | 500 or 600 mg/m² | IV | Days 1 and 8 |
Gastric cancer (platinum-containing regimen)
Gastric adenocarcinoma; part of a platinum-containing multi-drug regimen
Gastric adenocarcinoma; part of a platinum-containing multi-drug regimen [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Each cycle | |||
| Fluorouracil | 200 to 1000 mg/m² | Continuous 24-hour IV infusion | Number of days according to the regimen |
Pancreatic cancer (fluorouracil/leucovorin or a multi-drug regimen such as FOLFIRINOX)
Pancreatic adenocarcinomaCycle length: Every 2 weeks
Pancreatic adenocarcinoma [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Each cycle | |||
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 2400 mg/m² | Continuous 46-hour IV infusion | Starting on day 1 |
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Side effects
Common side effects
The most common side effects:
- Diarrhoea and mouth sores, each in more than half of patients with rapid injections [4].
- Nausea, vomiting, abdominal pain and tiredness [4].
- Hand-foot syndrome (red, sore, peeling palms and soles), mostly with the continuous pump and after a few weeks [1].
- Low white blood cells, which show up in blood tests [4].
For physicians
The current FDA label for fluorouracil has no adverse reaction frequency table. The type and severity of adverse reactions depend on the route of administration: hand-foot syndrome is more common with continuous infusion and usually appears after 8 to 9 weeks, whereas stomatitis is more common with bolus injection [1]. The table below shows the frequency of adverse reactions with bolus fluorouracil and leucovorin (Mayo regimen) in the comparator arm of the X-ACT trial [4].
| Adverse reaction | All grades | Grade 3 or 4 |
|---|---|---|
| Diarrhoea | 65% | 14% |
| Stomatitis | 60% | 14% |
| Nausea | 47% | 2% |
| Vomiting | 21% | 2% |
| Abdominal pain | 16% | 2% |
| Fatigue | 16% | 1% |
| Hand-foot syndrome | 9% | Less than 1% |
| Neutropenia (blood test) | — | 26% |
Source: FDA label for Xeloda, fluorouracil/leucovorin arm data in X-ACT [4]. Other adverse reactions reported after marketing: photosensitivity and skin hyperpigmentation, venous tract hyperpigmentation, nail changes and loss, dry and fissured skin, lacrimation and lacrimal duct stenosis, epistaxis [1].
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- Inherited DPD enzyme deficiency: in a small number of people, the drug causes very severe side effects from the first weeks (severe mouth sores, severe diarrhoea, infection). Talk to your doctor about a DPYD gene test before starting [1].
- Heart problems: chest pain or palpitations, especially while on the pump; report them straight away [1].
- Confusion, sleepiness or loss of balance on pump days [1].
- Severe diarrhoea, severe sores in the mouth and throat, or a temperature of 38 °C [1].
- With warfarin the risk of bleeding goes up; and harm to an unborn baby [1].
For physicians
Boxed warning: patients with complete DPD deficiency are at risk of early, severe and sometimes fatal toxicity (severe mucositis, diarrhoea, neutropenia and neurotoxicity). About 3 to 5% of the white population have partial and 0.2% complete DPD deficiency; DPYD testing before starting is recommended, although a negative test does not exclude all risk [1].
Other warnings in the label [1]:
- Cardiotoxicity: angina, myocardial infarction, arrhythmia and heart failure; continuous infusion and coronary artery disease are risk factors.
- Hyperammonaemic encephalopathy: confusion, mental agitation, ataxia or coma with raised blood ammonia, usually within 72 hours of starting the infusion.
- Neurological toxicity: acute cerebellar syndrome, confusion, ataxia and visual disturbance.
- Severe diarrhoea and severe mucositis (sores of the mouth, throat and oesophagus).
- Severe and sometimes fatal myelosuppression (neutropenia, thrombocytopenia and anaemia).
- Raised INR with warfarin.
- Embryo-fetal toxicity; allergic reactions and anaphylaxis have also been reported after marketing.
When should I call my doctor?
Call your doctor or go to the emergency department straight away if you have [1]:
- Chest pain, shortness of breath, dizziness or light-headedness
- Confusion, disorientation or any change in alertness; problems with balance or coordination; vision problems
- Fever or any sign of infection (check your temperature every day)
- Severe diarrhoea
- Painful mouth sores that have reduced how much you eat and drink
- Tingling or burning, redness, peeling, swelling, blisters or sores on the palms or soles
- Any pregnancy during treatment or up to 3 months after the last dose
Interactions, pregnancy and precautions
- Other medicines: tell your doctor about all your medicines, especially the blood thinner warfarin; fluorouracil increases its effect and blood clotting tests should be done regularly [1].
- Folic acid and leucovorin increase the toxicity of fluorouracil; deaths from severe enterocolitis, diarrhoea and dehydration have been reported in older people receiving weekly leucovorin and fluorouracil [4]. Take folate-containing supplements only on your doctor's advice [4].
- Contraception: women who could become pregnant and men with a partner who could become pregnant should use effective contraception during treatment and for 3 months after the last dose. The drug may reduce fertility in women and men [1].
- Breastfeeding: the label advises stopping breastfeeding during treatment [1].
- Tests: keep your blood test appointments regularly [1].
- Infusion pump: fluorouracil is a cytotoxic drug and is prepared following safety rules for hazardous drugs [1]; contact your treatment team if the pump leaks or has a problem.
Frequently asked questions
What is the difference between fluorouracil and capecitabine?
Capecitabine is an oral form that the body turns into fluorouracil, whereas fluorouracil is given into a vein [4]. As adjuvant treatment of colon cancer, oral capecitabine was at least as good as the bolus fluorouracil and leucovorin regimen [4].
What is the 46-hour pump for?
In common regimens for bowel and pancreatic cancer, after a rapid injection, most of the dose is given as a continuous infusion over 46 hours every 2 weeks, through a central venous catheter with a pump [1].
Why do they want a DPYD genetic test before starting?
Why is a blood test needed before every cycle?
Fluorouracil can lower blood counts a lot; white blood cells are usually lowest 9 to 14 days after the injection, and if the fall is severe the next cycle is delayed or the dose lowered [1].
Can this drug be given during pregnancy or breastfeeding?
Fluorouracil can harm an unborn baby; avoid pregnancy for 3 months after the last dose and do not breastfeed during treatment [1].
Scientific evidence
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Key studies
12 itemsDuration of Adjuvant Chemotherapy for Stage III Colon Cancer
Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Atezolizumab plus FOLFOX for Stage III Mismatch Repair-Deficient Colon Cancer
Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer
NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial
Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial
FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer
Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial
Clinical guidelines
4 itemsLocalised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Related cancer types
Treatment regimens (physicians)
References
9 referencesShow all references, 7 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer
- 3
- 4
- 5Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
- 6Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial
- 7
- 8FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
- 9FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer
This page is based on reputable scientific sources and was last updated on 27 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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