Folinic acid, fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI)

FOLFOXIRI is a cancer drug combination that includes folinic acid, fluorouracil (5FU), oxaliplatin and irinotecan. It is a treatment for bowel cancer that has spread to other parts of the body (advanced or metastatic bowel cancer).

What is FOLFOXIRI?

FOLFOXIRI is the name of a cancer drug combination that includes:

• FOL - folinic acid (also called leucovorin, FA or calcium folinate)
• F - fluorouracil (5FU)
• OX – oxaliplatin
• IRI - irinotecan

It is a treatment for bowel cancer that has spread to other parts of the body (advanced or metastatic bowel cancer).

How does FOLFOXIRI work?

Fluorouracil, oxaliplatin and irinotecan are chemotherapy drugs. They destroy quickly dividing cells, such as cancer cells. The drugs circulate around the body in the bloodstream. 

Folinic acid is not chemotherapy; you have it with fluorouracil to help it work better. 

How do you have FOLFOXIRI?

You have FOLFOXIRI as a drip into your bloodstream (intravenously).

You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a:

• central line
• PICC line
• portacath

How often do you have FOLFOXIRI?

You have FOLFOXIRI as cycles of treatment. This means that you have the drugs and then a rest to allow your body to recover.

Each cycle of treatment lasts 14 days (2 weeks). You might have up to 12 treatment cycles.

You have each cycle of treatment in the following way:

You then start your next cycle of treatment.

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working.

What are the side effects of FOLFOXIRI?

Side effects can vary from person to person. They also depend on what other treatment you are having. 

When to contact your team

Your doctor, pharmacist or nurse will go through the possible side effects. They will monitor you closely during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

• you have severe side effects

• your side effects aren’t getting any better

• your side effects are getting worse

• the side effects are affecting your daily life

Early treatment can help manage side effects better. 

We haven't listed all the side effects here. Remember it is very unlikely that you will have all of these side effects, but you might have some of them at the same time.

Common side effects

These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include:

Increased risk of infection

Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, headaches, feeling cold and shivery and generally unwell. You might have other symptoms depending on where the infection is.

Infections can sometimes be life threatening. You should contact your advice line urgently if you think you have an infection. 

Breathlessness and looking pale

You might be breathless and look pale due to a drop in red blood cells. This is called anaemia.

Bruising, bleeding gums or nose bleeds

This is due to a drop in the number of platelets in your blood. These blood cells help the blood to clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae).

Nerve problems

Numbness or tingling in fingers or toes is caused by oxaliplatin and is often temporary and can improve after you finish treatment. This is due to its effects on the nerves. The medical name for this is peripheral neuropathy.

Peripheral neuropathy can make it difficult to do fiddly things such as doing up buttons. It might be triggered and get worse with cold temperatures: for example, cold air, cold drinks, or touching anything cold.

Other nerve problems might include having abnormal sensation to different parts of the body such as a shock-like sensation passing down your arms.

Increased sensitivity to the cold

Oxaliplatin can make you more sensitive to the cold. It can affect your throat causing it to feel as though it is difficult to breathe and swallow. This can happen whilst you have oxaliplatin or within 2 hours of it finishing. It’s only temporary but can feel quite frightening.

Opening and closing the fridge or freezer, touching metal, eating or drinking cold foods and changes in temperature from the weather can trigger this.

It can help wearing gloves and avoid very cold food and drink for 24 hours before and after oxaliplatin.

Let your nurse know straight away if it's affecting your breathing and swallowing.

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. It might help to avoid fatty or fried foods, eat small meals and snacks and take regular sips of water. Relaxation techniques might also help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treat it once it has started.

Feeling or being sick can be severe for some people, even if you take anti sickness medicines. Contact your treatment team straight away if you have this. 

Tummy (abdominal) pain

Tell your doctor or nurse if you have this. They can check for the cause of the pain and give you medicine to help. 

Loose or watery poo (diarrhoea) 

You have diarrhoea if you've had 4 or more loose watery poos (stools) in 24 hours. 

Some people develop a set of side effects (syndrome) called cholinergic syndrome. As well as diarrhoea, you might have:

• increased sweating and chills
• dizziness
• increased saliva production
• eye problems such as watery eyes and changes to your eyesight
• stuffy nose
• tummy (abdominal) cramps

Your treatment team will give you instructions if diarrhoea starts more than 24 hours after your treatment. This includes taking anti diarrhoea medicines and drinking plenty of fluids. Ask them about soothing creams to apply around your back passage (anus). The skin in that area can get very sore and even break if you have severe diarrhoea.

Inflammation of the food pipe and back passage

An inflamed food pipe (oesophagus) can cause heartburn. Inflammation of the back passage (rectum) can cause diarrhoea. Other symptoms are pain, bleeding and discharge and the feeling that you want to pass a bowel movement.

Speak to your doctor or nurse if you have these symptoms.

Mouth sores and ulcers

Mouth sores and ulcers can be painful. It helps to keep your mouth and teeth clean, drink plenty of fluids and avoid acidic foods such as lemons. Chewing gum can help to keep your mouth moist. Tell your doctor or nurse if you have ulcers.

Allergic reaction

A reaction may happen during the infusion. Symptoms can include a skin rash, itching, swelling of the lips, face or throat, breathing difficulties, fever and chills. Your nurse will give you medicines beforehand to try to prevent a reaction. 

Loss of appetite

You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Taste changes

Taste changes may make you go off certain foods and drinks. You may also find that some foods taste different from usual or that you prefer to eat spicier foods. Your taste gradually returns to normal a few weeks after your treatment finishes.

Changes to the way your liver works

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working.

Difficulty breathing or a cough

You may have difficulty breathing and coughing. Let your doctor or nurse know straight away if this happens.

Heart problems

You might have a test called an electrocardiogram (ECG) . This is to check how well your heart is working. It can show some changes while having this treatment.

Rarely, you might have changes in your heart rhythm, a blockage to the blood flow to the heart (heart attack) and your heart not being able to pump properly because it has got bigger (dilative cardiomyopathy).

Feeling generally unwell

Speak to your doctor or nurse if you feel generally unwell after having this treatment.

Headaches

Tell your healthcare team if you keep getting headaches. They can give you painkillers to help.

Dizziness

This treatment might make you feel dizzy. Don’t drive or operate machinery if you have this.

Rigor

A sudden feeling of cold with shivering often with a rise in temperature and sweating.

Difficulty opening your bowels (constipation)

Constipation is easier to sort out if you treat it early. Drink plenty of fluids and eat as much fresh fruit and vegetables as you can. Try to take gentle exercise, such as walking. Tell your healthcare team if you think you are constipated. They can prescribe a laxative.

Changes to the level of sugar (glucose), potassium and sodium in your blood

The level of glucose and sodium in your blood might increase and the level of potassium might decrease. You have regular blood tests during treatment to check this. 

Pain

This treatment can cause pain in your back. Less commonly you might get pain in your muscles, bones, and your chest. Let your doctor or nurse know if you have any pain so that they can give you painkillers.

Skin changes

You might notice skin changes, such as dryness, itching and a rash. Rarely these drugs can also make your skin sensitive to sunlight. And patches of skin may get darker or lighter near veins. 

Tell your doctor if you have any rashes or itching. Don't go swimming if you have a rash because the chlorine in the water can make it worse.

If your skin gets dry or itchy, using unperfumed moisturising cream may help. Check with your doctor or nurse before using any creams or lotions. Wear a high factor sun block if you’re going out in the sun.

Soreness, redness and peeling on palms and soles of feet

The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome.

Moisturise your skin regularly. Your healthcare team will tell you what moisturiser to use.

Tiredness and weakness

You might feel very tired and as though you lack energy.

Various things can help you to reduce tiredness and cope with it, for example exercise. Some research has shown that taking gentle exercise can give you more energy. It is important to balance exercise with resting.

Hair loss

You could lose all your hair. This includes your eyelashes, eyebrows, underarms, legs and sometimes pubic hair. Your hair will usually grow back once treatment has finished but it is likely to be softer. It may grow back a different colour or be curlier than before. 

Swelling and pain at the drip site

Tell your nurse straight away if you have any pain, redness, or swelling around your drip site.

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include:

• eye problems - this includes problems with your vision and watery, red and itchy eyes (conjunctivitis). Rarely, you might have rapid eye movement from side to side.
• loss of body fluid (dehydration)
• low levels of calcium in the blood that might cause symptoms such as muscle cramps and weakness
• nerve problems causing muscle twitching and cramps
• feeling very low in mood (depressed)
• difficulty getting to sleep (insomnia)
• inflammation of the membranes covering the brain and spinal cord (meninges) causing symptoms similar to meningitis (stiff neck, unable to look at bright light and headache)
• blood in your poo due to ulcers in your gut and back passage (rectum) – let your team know if you notice this
• episodes of feeling warm and reddening of the skin (flushing)
• blood clots that can be life threatening; signs are pain, redness and swelling where the clot is. Feeling breathless can be a sign of a blood clot in the lung. Contact your advice line or doctor straight away if you have any of these symptoms
• high blood pressure that can give you headaches, nose bleeds, blurred or double vision or shortness of breath. Rarely you might get low blood pressure, this might cause you to feel dizzy, weak or even faint.
• hiccups
• heartburn or indigestion
• nail problems such as brittle, chipped and ridged nails
• kidney problems – you may pass blood when you wee, it may be painful and you might notice you are going more or less often than usual. Blood tests might show changes to how your kidneys are working
• a risk of falling
• weight loss
• runny nose

Rare side effects

These side effects happen in fewer than 1 in 100 people (less than 1%). You might have one or more of them. They include:

• hearing changes - more rarely this can cause loss of hearing
• feeling very happy (euphoria)
• feeling confused or nervous
• shaking and trembling, stiffness and slow movement (symptoms of Parkinson's disease)
• weakness in your legs or an increase in the muscle tone of your legs and feet causing them to be stiff
• feeling very sleepy and sleeping for longer periods of time
• a serious blood clotting condition that can cause you to bleed (disseminated intravascular coagulation). Tell your team straight away if you notice any signs or symptoms such as bleeding, bruising, shortness of breath, feeling as though you may faint or you are confused.
• imbalance of substances in your blood (metabolic acidosis) – this can cause confusion, tiredness, shortness of breath and headaches
• difficulty in speaking
• posterior reversible encephalopathy syndrome (PRES) - a rare disorder of the nerves causing headaches, fits, confusion and changes in vision. Contact your healthcare team straight away if you have these symptoms. This condition is reversible.
• slowing or blockage of the gut

What else do I need to know?

DPD deficiency

Between 2 and 8 out of 100 people (2 to 8%) have low levels of an enzyme called dihydropyrimidine dehydrogenase (DPD) in their bodies. A lack of DPD can mean you’re more likely to have severe side effects from capecitabine or fluorouracil. It might take you a bit longer to recover from the chemotherapy. These side effects can rarely be life threatening.

Before starting treatment with capecitabine or fluorouracil you have a blood test to check levels of DPD. So you may start treatment with a lower amount (dose) of the drug or have a different treatment. Your doctor or nurse will talk to you about this.

Other medicines, foods and drinks

Cancer drugs can interact with some other medicines and herbal products. Tell your doctor or pharmacist about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies.

Alcohol

Check with your doctor to see if drinking alcohol may harm you while having this treatment. 

Sodium

Fluorouracil (5FU) contains sodium (salt). You might need to take account of this if you are on a controlled sodium diet. Tell your doctor if you are on a low salt diet.

Loss of fertility

You may not be able to become pregnant or get someone pregnant after treatment with these drugs. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.    

Contraception and pregnancy

This treatment may harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you're having treatment and for at least 6 months afterwards.

Talk to your doctor or nurse about effective contraception before starting treatment. Let them know straight away if you or your partner become pregnant while having treatment. 

Breastfeeding

Don’t breastfeed during this treatment. This is because the drugs may come through in your breast milk.

Treatment for other conditions

If you are having tests or treatment for anything else, always mention your cancer treatment. For example, if you are visiting your dentist.

Immunisations

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and one of the shingles vaccines called Zostavax.

You can have:

• other vaccines, but they might not give you as much protection as usual
• the flu vaccine (as an injection)
• the coronavirus (COVID-19) vaccine - talk to your doctor or pharmacist about the best time to have it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

More information about this treatment

For further information about this treatment and possible side effects go to the electronic Medicines Compendium (eMC) website. You can find the patient information leaflet on this website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.