5-FU (Fluorouracil) Chemotherapy

Last updated: October 9, 2026 | Reviewed by the Oncol.net editorial team

Overview

5-Fluorouracil, commonly abbreviated as 5-FU, is an antimetabolite chemotherapy drug that disrupts cancer cell growth and division. It is classified as a pyrimidine analog, meaning it mimics natural building blocks of DNA and RNA but contains a fluorine atom that prevents proper cell replication. 5-FU has been in clinical use for over 65 years and continues to be essential in treating multiple cancer types.

The drug can be given as a rapid intravenous push (bolus) or as a continuous infusion over 24-48 hours. Continuous infusion is more common in modern regimens and generally has a different side effect profile compared to bolus administration. 5-FU is rarely given alone; it is almost always combined with other chemotherapy agents and often with leucovorin (folinic acid), which enhances its anti-cancer effects.

How 5-FU Works

Mechanism of Action

• Thymine synthesis inhibition: 5-FU is converted in cells to active metabolites that block thymidylate synthase, an enzyme essential for making thymine (a DNA building block). Without thymine, cells cannot replicate their DNA and divide.
• RNA incorporation: 5-FU metabolites also get mistakenly incorporated into RNA molecules, disrupting RNA function and protein synthesis.
• DNA incorporation: To a lesser extent, 5-FU metabolites are incorporated into DNA, causing strand breaks and dysfunction.
• Cell cycle specificity: 5-FU primarily affects cells in S-phase (DNA synthesis phase), making it most effective against rapidly dividing cancer cells.

Leucovorin Enhancement

Leucovorin (folinic acid) is almost always given with 5-FU because it:

• Stabilizes the bond between 5-FU metabolites and thymidylate synthase
• Increases the duration of enzyme inhibition
• Enhances anti-cancer activity by 3-5 fold
• Does not significantly increase toxicity

Cancer Types Treated with 5-FU

Primary Indications (FDA-Approved)

• Colorectal cancer: Standard component of most regimens (FOLFOX, FOLFIRI, CAPEOX)
  • Adjuvant treatment after surgery
  • First-line treatment for metastatic disease
  • Combination with oxaliplatin or irinotecan
  • 5-FU-based chemotherapy is backbone of colon cancer treatment
• Gastric (stomach) and gastroesophageal junction cancer:
  • Perioperative chemotherapy (before and after surgery)
  • Palliative treatment for advanced disease
  • Often combined with platinum agents (cisplatin, oxaliplatin)
• Pancreatic cancer:
  • Part of FOLFIRINOX regimen (5-FU + leucovorin + irinotecan + oxaliplatin)
  • One of the most effective regimens for metastatic pancreatic cancer
• Breast cancer:
  • Historically part of CMF regimen (cyclophosphamide, methotrexate, 5-FU)
  • Less commonly used now due to more effective newer agents
• Esophageal cancer:
  • Combined with cisplatin and radiation (trimodal therapy)
  • Palliative chemotherapy for advanced disease
• Anal cancer:
  • Combined with mitomycin C and radiation (Nigro protocol)
  • Curative in majority of cases
• Head and neck cancer:
  • Combined with cisplatin and radiation
  • Induction chemotherapy or concurrent with radiation

Other Uses

• Hepatobiliary cancers (biliary tract, gallbladder)
• Cervical cancer
• Skin cancers (topical formulation for actinic keratosis and superficial basal cell carcinoma)

How 5-FU is Given

Route of Administration

• Intravenous (IV): Standard for cancer treatment
  • Bolus doses can go through a cannula; 46-hour pump infusions are given through a central line (port or PICC line)
  • There is no 5-FU pill. The oral alternative is capecitabine (Xeloda), a prodrug the body converts into 5-FU
• Topical cream (Efudex 5%, Carac 0.5%, Tolak 4%): For actinic keratoses and some superficial basal cell carcinomas, not for internal cancers. Keep the cream away from pets: dogs that lick or chew a tube can be fatally poisoned.

Administration Methods

• Bolus injection: Rapid IV push over 1-2 minutes
  • Used in older regimens (Mayo Clinic regimen, Roswell Park regimen)
  • Higher risk of myelosuppression (low blood counts)
  • Less commonly used today
• Continuous infusion: Slow IV infusion over 46-48 hours
  • Most common method in modern regimens (FOLFOX, FOLFIRI)
  • Requires ambulatory infusion pump (small portable pump worn at home)
  • Higher risk of hand-foot syndrome and mucositis
  • Lower risk of severe myelosuppression compared to bolus

Common Regimens

Infusion Pump Management

For continuous infusion regimens:

• Small portable pump (about the size of a pager) worn in a pouch or fanny pack
• Connected to central line (port or PICC)
• Programmed to deliver 5-FU continuously over 46-48 hours
• Patients go home with the pump and return to clinic for disconnection
• Can shower (waterproof pump cover available), but cannot swim or submerge
• Sleep, eat, and perform most daily activities normally
• Keep pump at body temperature (don't expose to extreme heat or cold)

Dosing

Factors Affecting Dose

• Body surface area (BSA): Calculated from height and weight (typical unit: mg/m²)
• Regimen: Dose varies by specific protocol
• Bolus vs infusion: Continuous infusion uses higher total doses but over longer time
• Combination drugs: May require dose adjustments
• Organ function: Kidney and liver function
• Prior toxicity: Doses reduced for significant side effects
• DPD status: Patients with DPD deficiency require major dose reduction or alternative therapy

Typical Doses (Examples)

• FOLFOX/FOLFIRI: 400 mg/m² IV bolus, then 2400-3000 mg/m² continuous infusion over 46 hours
• Bolus regimen: 425-500 mg/m² IV daily for 5 days every 4 weeks (older protocol)
• Weekly regimen: 500-600 mg/m² IV weekly

Side Effects

Side effect profile depends significantly on administration method (bolus vs continuous infusion).

Common Side Effects (Occur in >25% of Patients)

Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia)

• More common with continuous infusion (30-40%) than bolus (5-10%)
• Symptoms:
  • Redness, swelling, tingling, or numbness of palms and soles
  • Tenderness and sensitivity to touch
  • Peeling, blistering, or cracking skin in severe cases
  • Difficulty walking, gripping objects, or writing
• Usually appears after 2-3 cycles
• Management:
  • Keep hands and feet cool (avoid hot water, heating pads)
  • Moisturize frequently with thick creams (urea-based or petroleum jelly)
  • Avoid tight shoes and prolonged pressure on hands/feet
  • Pyridoxine (vitamin B6) 100-150 mg daily may help (limited evidence)
  • Dose reduction if severe (Grade 2-3)

Mucositis (Mouth Sores)

• Incidence: 30-40% (higher with bolus dosing)
• Symptoms: Painful sores in mouth and throat, difficulty eating/swallowing
• Onset: Usually 5-10 days after treatment
• Management:
  • Oral cryotherapy (ice chips during bolus infusion): reduces risk by 40-50%
  • Excellent oral hygiene (soft toothbrush, gentle brushing 4× daily)
  • Rinse with salt and baking soda solution every 2-4 hours
  • Avoid spicy, acidic, hot, or rough foods
  • Magic mouthwash for pain relief
  • Prescription analgesics if severe

Diarrhea

• Incidence: 30-50% (especially with FOLFIRI due to irinotecan)
• Can be severe and require hospitalization if not managed promptly
• Management:
  • Start loperamide at first sign (4 mg initially, then 2 mg after each loose stool)
  • BRAT diet (bananas, rice, applesauce, toast)
  • Hydration (replace each stool with 8 oz fluid)
  • Avoid dairy, high-fiber foods, caffeine, alcohol
  • Seek medical attention if >6 stools/day, fever, severe cramping, or blood in stool

Nausea and Vomiting

• Incidence: 30-50%
• 5-FU alone is low-moderate emetogenic (often combined with highly emetogenic drugs like cisplatin)
• Management:
  • Preventive anti-nausea medications (ondansetron, metoclopramide, prochlorperazine)
  • Small, frequent meals
  • Avoid strong odors, greasy or spicy foods
  • Ginger, acupressure, or medical marijuana may help

Fatigue

• Incidence: 40-60%
• Cumulative, worsens with multiple cycles
• Management:
  • Balance rest with light exercise
  • Energy conservation techniques
  • Treat contributing factors (anemia, depression, poor sleep)

Less Common but Serious Side Effects

Myelosuppression (Low Blood Counts)

• More common with bolus than continuous infusion
• Nadir (lowest point): 7-14 days after treatment
• Neutropenia (low white blood cells): Increased infection risk
  • Fever ≥100.4°F requires immediate medical attention
  • G-CSF (Neupogen) may be given if severe or recurrent
• Thrombocytopenia (low platelets): Bleeding/bruising risk
• Anemia (low red blood cells): Fatigue, shortness of breath

Cardiotoxicity

• Rare but potentially life-threatening (incidence: 1-5%)
• More common with continuous infusion and in patients with pre-existing heart disease
• Manifestations:
  • Chest pain (angina) - most common, occurs during or shortly after infusion
  • Arrhythmias (irregular heartbeat)
  • Heart attack (myocardial infarction)
  • Cardiomyopathy (rare)
• Usually reversible if 5-FU is stopped
• Patients with history of coronary artery disease require close monitoring
• If chest pain occurs, 5-FU should be stopped and not restarted

Cerebellar Toxicity (Neurological)

• Rare (<1%) but serious
• Symptoms: Loss of coordination, difficulty walking, slurred speech, tremors
• May be irreversible
• 5-FU must be discontinued permanently if this occurs

Watery Eyes (Excessive Tearing)

• Incidence: 10-20%
• Due to nasolacrimal duct stenosis
• Bothersome but not dangerous
• May improve after treatment ends or may be permanent

Rare Side Effects

• Photosensitivity (increased sun sensitivity)
• Hyperpigmentation of skin or nails
• Nail changes (darkening, lifting, loss)
• Skin rash
• Liver enzyme elevations (usually mild)
• Allergic reactions (very rare)

DPD Deficiency

What is DPD?

Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for breaking down 5-FU in the body. Over 80% of administered 5-FU is normally metabolized by DPD. Deficiency in this enzyme leads to toxic accumulation of 5-FU.

Prevalence and Genetics

• Partial DPD deficiency: 3-5% of population (reduced enzyme activity)
• Complete DPD deficiency: 0.1-0.5% (absent or minimal enzyme activity)
• Caused by mutations in DPYD gene (most common: DPYD*2A)
• More common in certain populations

Clinical Consequences

• Complete (or near-complete) deficiency: the FDA label states that no 5-FU dose has been shown to be safe, and the drug should generally be avoided in favour of a different treatment
  • Toxicity can be severe and early: mucositis, diarrhoea, very low blood counts and neurological symptoms, sometimes within the first cycle
• Partial deficiency (intermediate metabolisers): increased risk of severe toxicity
  • Pharmacogenetic guidelines (CPIC) recommend starting at a reduced dose, commonly about half the standard dose, and then increasing if it is well tolerated
  • Close monitoring during the first cycles

Testing for DPD Deficiency

• Genetic testing (DPYD genotyping):
  • A blood or saliva test looking for the best-studied DPYD variants (for example DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A/HapB3)
  • A negative result lowers, but does not remove, the risk: rarer variants are not covered by standard panels, and the common panels were developed mainly in people of European ancestry
• Phenotypic testing (blood uracil level):
  • Measures uracil, which builds up when DPD activity is low; used routinely in some European countries
• Where guidance stands: the European Medicines Agency has recommended testing before fluoropyrimidine treatment since 2020. In the US, the FDA updated the fluorouracil and capecitabine labels (2024–2025) to describe the risk in more detail and to advise clinicians to consider DPYD testing before treatment unless immediate treatment is needed. NCCN guidance has also moved towards discussing pre-treatment testing. Results usually take several days, so ask about it early.

Monitoring During Treatment

Before Each Treatment Cycle

• Complete blood count (CBC): Check white blood cells, platelets, hemoglobin
  • Treatment may be delayed if counts too low
  • ANC (absolute neutrophil count) should be ≥1500
  • Platelets should be ≥100,000
• Comprehensive metabolic panel: Kidney and liver function, electrolytes
• Assessment of side effects: Hand-foot syndrome, mucositis, diarrhea
• Performance status: Ability to perform daily activities

Dose Modifications

Doses are reduced or treatment delayed based on toxicity:

• Grade 2 hand-foot syndrome: 25% dose reduction
• Grade 3 hand-foot syndrome: Hold until improved to Grade 1, then 50% dose reduction
• Grade 3-4 mucositis or diarrhea: Hold treatment, reduce dose by 25-50% when resumed
• Neutropenic fever: Hold treatment, add G-CSF, reduce dose by 25% when resumed
• Cardiotoxicity: Discontinue 5-FU permanently

Drug Interactions

Significant Interactions

• Leucovorin (folinic acid): Intentional interaction - enhances 5-FU efficacy
• Warfarin: 5-FU increases warfarin effect, increasing bleeding risk
  • Monitor INR closely
  • Warfarin dose may need reduction
• Phenytoin: 5-FU increases phenytoin levels (seizure medication)
  • Monitor phenytoin levels
• Metronidazole: May increase 5-FU toxicity (avoid if possible)
• Allopurinol: May decrease 5-FU effectiveness
• Live vaccines: Should be avoided during 5-FU treatment (immunosuppression risk)

Foods and Supplements

• No specific food restrictions during treatment
• Avoid excessive vitamin B9 (folic acid) supplements (may enhance toxicity)
• Discuss all supplements with oncology team before taking

Pregnancy and Fertility

Pregnancy

• Pregnancy Category D: Can cause fetal harm
• Contraindicated during pregnancy except in life-threatening situations where benefit outweighs risk
• Effective contraception required during treatment and for 3-6 months after
• Both men and women should use contraception

Breastfeeding

• Unknown if 5-FU passes into breast milk, but likely
• Breastfeeding should be discontinued during 5-FU treatment

Fertility

• May cause temporary or permanent infertility in both men and women
• Sperm banking or egg/embryo preservation should be discussed before treatment if fertility is desired
• Risk of permanent infertility increases with cumulative dose and patient age

Frequently Asked Questions

What is 5-FU chemotherapy?

5-FU (5-fluorouracil, or fluorouracil) is an antimetabolite chemotherapy drug. It looks like one of the building blocks cells use to make DNA and RNA, so dividing cancer cells take it up and can no longer copy themselves. It is used mainly for bowel, stomach, oesophageal, pancreatic, anal and head and neck cancers, almost always together with other drugs such as leucovorin, oxaliplatin or irinotecan, or with radiotherapy.

How is 5-FU given?

Into a vein. In the common FOLFOX and FOLFIRI regimens you receive a short bolus injection in clinic, then a 46-hour infusion from a small portable pump connected to a port or PICC line, which you wear at home and have disconnected two days later. Cycles repeat every 14 days. Some regimens give 5-FU as a continuous infusion during radiotherapy, and older regimens give bolus doses only. There is no 5-FU tablet; the oral alternative is capecitabine, which the body converts into 5-FU.

What do FOLFOX, FOLFIRI and FOLFIRINOX mean?

They are abbreviations for combinations that contain 5-FU. FOL stands for folinic acid (leucovorin), F for fluorouracil, OX for oxaliplatin and IRI for irinotecan. FOLFOX and FOLFIRI are mainly used for colorectal cancer, and FOLFIRINOX (all four drugs) mainly for pancreatic cancer. CAPOX (also called XELOX) is the version that uses capecitabine tablets instead of 5-FU infusions.

Is Efudex cream the same as 5-FU chemotherapy?

It is the same drug, fluorouracil, but used very differently. Efudex (5%), Carac (0.5%) and Tolak (4%) are creams applied to the skin for actinic keratoses and some superficial basal cell carcinomas. Very little reaches the bloodstream, so the side effects are mostly local redness, crusting and soreness. The intravenous drug is used for internal cancers. Rarely, people with complete DPD deficiency have had serious reactions even to the cream, and the cream is highly toxic to dogs and cats that lick or chew it.

Should I be tested for DPD deficiency before starting 5-FU?

Ask your oncology team about it. About 3 to 5 percent of people have partial DPD deficiency and a much smaller number have complete deficiency, which can make standard doses of 5-FU or capecitabine dangerous. The FDA label now advises clinicians to consider testing for DPYD gene variants before treatment unless it cannot be delayed, and testing has been recommended in Europe since 2020. A positive result usually means a lower starting dose or a different drug. A negative result does not rule out every cause of severe toxicity, so early side effects still need to be reported promptly.

Is there an antidote for 5-FU?

Yes. Uridine triacetate (Vistogard) is an FDA-approved oral antidote for 5-FU or capecitabine overdose and for early-onset severe or life-threatening toxicity. It must be started within 96 hours of the end of the 5-FU dose, which is why severe diarrhoea, mouth sores, chest pain or confusion early in a cycle should be reported straight away.

Will I lose my hair from 5-FU?

Usually not. Hair thinning can happen with 5-FU, but complete hair loss is uncommon when it is used alone. Drugs given with it can cause more hair loss, particularly irinotecan in FOLFIRI and FOLFIRINOX; oxaliplatin in FOLFOX tends to cause mild thinning at most. See our hair loss guide.

What is hand-foot syndrome and is it dangerous?

Hand-foot syndrome (palmar-plantar erythrodysesthesia) is redness, tenderness, peeling or blistering of the palms and soles. It is more common with infusional 5-FU and capecitabine than with bolus 5-FU. It is not life-threatening, but severe cases make walking and gripping difficult. Keeping hands and feet cool, moisturising with urea-based creams and avoiding friction help, and the dose is reduced or paused if it becomes painful. It improves once the dose is lowered or treatment stops.

What if I have severe diarrhoea or mouth sores?

Contact your oncology team immediately; see when to call your oncology team. Diarrhoea with more than four to six extra stools a day, diarrhoea with fever, or mouth sores that stop you eating or drinking can lead to dehydration and infection. These are dose-limiting side effects, so the next dose is usually reduced, and early severe toxicity may need hospital care and sometimes uridine triacetate.

Why is 5-FU given over 46 hours instead of all at once?

5-FU is cleared from the blood within minutes and mainly harms cells that are copying their DNA at that moment. A 46-hour infusion keeps the drug present across more of the cell cycle, which improves its effect on the tumour and causes fewer severe drops in blood counts than large bolus doses. The trade-off is more hand-foot syndrome and mouth soreness.

How long does 5-FU keep killing cancer cells after the infusion ends?

5-FU itself disappears from the bloodstream very quickly — its half-life is only about 10 to 20 minutes. The active metabolites formed inside cells persist far longer, which is why the drug keeps working after the pump is disconnected. Cell killing happens during the S-phase of division, so cancer cells are hit as they attempt to replicate over the following days rather than all at once. This is also the reason 5-FU is given in repeated cycles: each cycle catches a further wave of dividing cells. Blood counts reflect this delayed effect, reaching their lowest point (nadir) roughly 9 to 14 days after treatment.

How soon should tumour markers such as CEA or CA 19-9 fall on 5-FU?

Markers usually take two to three cycles — roughly six to eight weeks — before a meaningful downward trend is visible, and a transient rise after the first cycle is not unusual as tumour cells break down. Individual readings fluctuate, so oncologists look at the trend across several measurements alongside imaging rather than reacting to a single value. Response is normally formally assessed with a CT scan after about two to three months of treatment.

What should I do if my pump stops working or alarms?

Check the display and the instructions from your infusion unit, look for kinks or clamps on the line, and call the 24-hour number you were given. Do not disconnect the pump yourself unless you have been trained and told to. If the pump or line leaks, follow your unit's spill instructions and wear gloves to clean it up.

Can 5-FU be given if kidney function is poor?

Generally yes. 5-FU is broken down mainly by the DPD enzyme rather than the kidneys, so no routine dose reduction is specified for reduced kidney function, unlike capecitabine, which needs a lower dose in moderate kidney impairment and is avoided when creatinine clearance is below 30 mL/min. Your team will still review the whole regimen, especially any platinum partner such as cisplatin.

Can I drink alcohol or have vaccines while receiving 5-FU?

Small amounts of alcohol are not known to interact with 5-FU, but alcohol can worsen nausea, diarrhoea and mouth sores, so many people avoid it during treatment. Inactivated vaccines such as the flu and COVID vaccines are recommended; live vaccines should be avoided during treatment and for a period afterwards. Check timing with your team.

How long will I be on 5-FU?

It depends on the cancer and the goal of treatment. After surgery for colon cancer, chemotherapy usually lasts 3 to 6 months. For advanced cancer it may continue as long as it is working and tolerated, sometimes with breaks. Your oncologist will explain the plan for your situation.

Can I switch from IV 5-FU to capecitabine tablets?

Often, yes. Capecitabine (Xeloda) is converted into 5-FU in the body and can replace infusional 5-FU in several regimens, such as CAPOX instead of FOLFOX or capecitabine with radiotherapy for rectal cancer. It avoids the pump but involves tablets twice a day, causes more hand-foot syndrome, and carries the same DPD risk. Whether it suits you depends on the regimen, kidney function and your ability to take tablets reliably.

Sources and References

• National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology
• American Society of Clinical Oncology (ASCO) Guidelines
• 5-Fluorouracil Prescribing Information (FDA-approved label)
• Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clinical Pharmacokinetics. 1989
• European Medicines Agency. EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine (2020)
• U.S. Food and Drug Administration. Fluorouracil injection and capecitabine prescribing information, Warnings and Precautions: dihydropyrimidine dehydrogenase (DPD) deficiency (labeling updates 2024–2025)
• U.S. Food and Drug Administration. Vistogard (uridine triacetate) prescribing information
• Clinical Pharmacogenetics Implementation Consortium (CPIC). Guideline for DPYD genotype and fluoropyrimidine dosing (2017 update and later revisions)
• National Cancer Institute. Fluorouracil Injection and Fluorouracil Topical drug information summaries
• Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nature Reviews Cancer. 2003