Fluorouracil

Uses	Colorectal, breast, stomach, pancreatic and head and neck cancers; actinic keratoses and some skin cancers
Therapy	Anti-Neoplastic
Side Effects	Mouth ulcers, diarrhoea, low blood counts, skin irritation where applied

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Molecule Description

Fluorouracil is an anti-cancer medicine belonging to a group called antimetabolites. It is used in two very different ways. Given as an injection or a drip into a vein, it treats cancers inside the body. Applied to the skin as a cream or solution, it treats sun-damaged skin patches and certain surface skin cancers. As an infusion, Fluorouracil is used for cancer of the colon and rectum, and for breast, stomach, pancreatic and head and neck cancers. It is usually given alongside other anti-cancer medicines, by a doctor or nurse in a hospital or clinic. Applied to the skin, it is used for actinic (solar) keratoses and for some superficial skin cancers. However it is given, Fluorouracil works in the same way. It blocks an enzyme that cells need to make DNA, so cells that divide quickly cannot multiply and die off. Cancer cells divide quickly, which is why they are affected most, but some healthy tissues divide quickly too — the lining of the mouth and gut, and the bone marrow — which is where many of the side effects come from. Before treatment starts, tell your doctor if you have a deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme breaks Fluorouracil down in the body. If you lack it, even ordinary amounts can cause severe and sometimes life-threatening side effects, and your doctor may test for this first. Fluorouracil can harm an unborn baby and must not be used in pregnancy. Tell your doctor about every medicine you take. Brivudine and sorivudine, used for shingles and chickenpox, must not be taken anywhere near this medicine, as the combination can be fatal.

Uses

Cancer of the colon and rectum
Breast cancer
Stomach (gastric) cancer
Pancreatic cancer
Head and neck cancers
Actinic (solar) keratoses — rough, scaly patches caused by long-term sun exposure
Certain superficial skin cancers, when applied to the skin

Contraindications

When should one not use Fluorouracil

If you are allergic to Fluorouracil
If you have a complete deficiency of the DPD enzyme
During pregnancy and breastfeeding
If you are taking, or have recently taken, brivudine or sorivudine for shingles or chickenpox — the combination can be fatal
If your bone marrow is severely suppressed, or you have a serious infection, when it is given into a vein
If you are in a poor nutritional state or severely weakened by illness
On broken skin, mucous membranes, or near the eyes, when applied to the skin

Side effects

Common side effects of this drug are:

When given into a vein:
Sore mouth and mouth ulcers
Diarrhoea
Nausea and vomiting
Loss of appetite
Low white cells, red cells and platelets, raising the risk of infection, tiredness and bleeding
Redness, soreness or peeling of the palms and soles (hand-foot syndrome)
Thinning of the hair
Watery eyes and sensitivity to light
Darkening of the skin, nails or the veins used for treatment
Chest pain or changes in heart rhythm, which are uncommon but need urgent attention
When applied to the skin:
Burning or stinging where it is applied
Redness, swelling and discoloration of the treated skin
Crusting, scaling or weeping of the treated area
Itching, pain or soreness at the site
Greater sensitivity of treated skin to sunlight
Tell your doctor straight away about severe diarrhoea, a fever or sore throat, mouth ulcers that stop you eating or drinking, unusual bruising or bleeding, chest pain, or a skin reaction that spreads beyond the area you treated

Precautions and Warnings

Pregnancy

No. Fluorouracil can harm an unborn baby and must not be used during pregnancy. If you could become pregnant, use effective contraception during treatment and for the period your doctor advises afterwards. Men should also use contraception, as advised. Tell your doctor immediately if you become pregnant during treatment.

Breast Feeding

No. Breastfeeding should be stopped during treatment with Fluorouracil and for the period your doctor advises afterwards, because of the risk to the baby.

Driving

When Fluorouracil is given as an infusion it can cause tiredness, nausea, watery eyes or blurred vision. Do not drive or use machinery if you are affected. When it is applied to the skin, it is not expected to affect your alertness or your ability to drive.

Alcohol

No specific interaction between alcohol and Fluorouracil has been established. Alcohol can make nausea, tiredness and a sore mouth worse, so discuss it with your doctor.

Other General Warnings

Talk to your doctor if

You have, or may have, a deficiency of the DPD enzyme — this can cause severe toxicity and your doctor may test for it before treatment.
You are taking or have recently taken brivudine or sorivudine.
You develop severe diarrhoea, or mouth ulcers that stop you eating and drinking.
You develop a fever, sore throat or any sign of infection.
You notice unusual bruising or bleeding.
You get chest pain or notice your heartbeat has changed.
You are having regular blood tests — keep these appointments, as your blood counts, liver and kidneys need monitoring during infusion treatment.
Treated skin becomes red, irritated and scaly in the first few weeks of skin treatment — this is expected, but tell your doctor if it is severe or spreads beyond the area you treated.
You are going out in the sun — treated skin burns more easily, so cover up and use sunscreen, and avoid sunbeds.
You are pregnant, planning a pregnancy, or breastfeeding.
Keep this medicine away from your eyes, eyelids, nose and mouth, and out of the reach of children and pets.

Mode of Action

How Does It Work?

Fluorouracil is an antimetabolite. Inside the body it is converted into active forms that block an enzyme called thymidylate synthase. Cells need this enzyme to make thymidylate, one of the building blocks of DNA. Without it, cells cannot copy their DNA properly and stop dividing. It is also taken up into RNA, which disrupts how cells make proteins. Fast-dividing cells, including cancer cells, are affected most. This is the same whether the medicine is given into a vein or applied to the skin.

Interactions

Interactions with other medicines

Brivudine and sorivudine, used for shingles and chickenpox, must not be used with Fluorouracil. They stop the body breaking it down and the combination can cause fatal toxicity. A gap is needed between the two medicines — your doctor will advise.
Warfarin and other blood thinners: Fluorouracil can increase their effect, so your clotting will need closer monitoring.
Phenytoin: levels can rise, increasing the risk of side effects.
Folinic acid (leucovorin) is sometimes given deliberately with Fluorouracil to make it work better, but it also increases its side effects.
Other chemotherapy medicines and radiotherapy add to the effect on the bone marrow and the lining of the mouth and gut.
Metronidazole and cimetidine can increase the amount of Fluorouracil in the body.
Live vaccines should be avoided during treatment.
When using it on the skin, do not apply other creams, ointments or cosmetic products to the treated area unless your doctor approves.
Tell your doctor about every medicine, supplement and herbal product you take.

Interactions with food items

No specific food interactions have been established with Fluorouracil. If you are having it as an infusion, drink enough fluids and eat as well as you can manage; tell your team if a sore mouth or diarrhoea is making this difficult. If you are using it on the skin, continue your normal diet unless your doctor advises otherwise.

Dosage

Overdose

When given into a vein, Fluorouracil is administered by trained staff, so an overdose is unlikely. If one occurs, the effects are an exaggeration of the usual side effects — severe mouth ulcers, diarrhoea, bleeding and a sharp fall in blood counts — and you would be monitored closely and treated in hospital. An antidote exists for use in this situation and your team will decide if it is needed. The cream or solution is applied to the skin, so overdose is uncommon, but if it is swallowed, or gets into the eye, seek emergency medical help immediately and flush the eye with plenty of water.

Missed a Dose

Infusions are scheduled and given by your treating team. If you miss an appointment, contact the clinic to rearrange it rather than trying to make it up. If you are applying it to the skin and miss an application, apply it when you remember, unless it is nearly time for the next one. Do not apply a double amount to make up for a missed application.

Frequently Asked Questions (FAQs)

It depends on what is being treated. Cancers inside the body need the medicine to travel in the bloodstream, so it is given as an injection or drip. Sun-damaged patches and some surface skin cancers can be treated by putting the medicine directly on the skin, which keeps most of it where it is needed.

DPD is an enzyme that breaks fluorouracil down after it has done its job. Some people are born with little or none of it. In them the medicine builds up and can cause severe, sometimes life-threatening side effects, even at ordinary amounts. Your doctor may test for this before starting treatment.

Yes, when the cream or solution is used on the skin. Redness, swelling, irritation and scaling of the treated area are expected in the first few weeks and show the medicine is working on the damaged cells. Do not stop early unless your doctor tells you to, but do report a severe reaction or one that spreads beyond the treated area.

A sore mouth and mouth ulcers are common. Keep your mouth clean with a soft brush, rinse as your team advises, and avoid very hot, spicy or acidic food. Tell your team early — if ulcers stop you eating or drinking, your treatment may need adjusting.

Yes. Fluorouracil makes skin more sensitive to sunlight, particularly skin you have treated with the cream or solution. Avoid strong sun and sunbeds, cover up, and use sunscreen on exposed skin.

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