Aflibercept, and folinic acid, fluorouracil and irinotecan (FOLFIRI)

Aflibercept and FOLFIRI is the name of a combination of cancer drugs. You have:

• aflibercept - (af-lib-er sept). It is also known as Zaltrap

• folinic acid - (foh-lin-ik ass-id). It is also called leucovorin, calcium folinate or FA

• fluorouracil - (floor-oh-yoor-uh-sil). It is also called 5FU

• irinotecan - (i-rin-o-te-can)

It is a treatment for advanced bowel cancer. Bowel cancer is also known as colorectal cancer. 

You might have this if you’ve previously had a treatment that includes oxaliplatin. But the cancer has:

• not responded to the treatment

• come back after treatment

How does aflibercept and FOLFIRI work?

Aflibercept is a type of targeted cancer drug . Cancers need a blood supply to survive and grow. Aflibercept stops the cancer from growing new blood vessels. It does this by reducing oxygen and nutrients to the cancer. This helps to stop or slow down the growth of the cancer.

Fluorouracil and irinotecan are chemotherapy drugs. They destroy quickly dividing cells, such as cancer cells.

Folinic acid is not a chemotherapy. But you often have it with fluorouracil to help it work better.   

How do you have aflibercept and FOLFIRI?

You have aflibercept, folinic acid, 5FU, and irinotecan 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 aflibercept and FOLFIRI?

You have aflibercept and FOLFIRI 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 2 weeks (14 days). You continue to have this as long as it’s working and the side effects are not too bad.

Exactly how you have your drugs may depend on your treatment centre and your circumstances.

The following is an example:

Then you start the cycle again.

5FU pump

You have the fluorouracil (5FU) through a small portable pump. This means you can go home with it. The pump slowly puts the fluid into your bloodstream (infusion). You can keep the pump in a small bag or attach it to a belt. You’ll need to go back to the hospital after the second day of your treatment to have the pump removed. Or sometimes a chemotherapy nurse may be able to do it for you at home.

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.

Before starting treatment with fluorouracil (5FU) you have a blood test to check levels of an enzyme called dihydropyrimidine dehydrogenase (DPD). A low DPD level means you are more likely to have severe side effects from this chemotherapy, so you may start treatment with a lower amount (dose) of the drug or have a different treatment. Your doctor, nurse or pharmacist will talk to you about this.

What are the side effects of aflibercept and FOLFIRI?

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. Talk to your healthcare team if you have any new symptoms that you think might be a side effect of your treatment.

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, cough, headaches, feeling cold and shivery, pain or burning feeling when weeing, or generally feeling 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. 

Bruising, bleeding gums or nosebleeds

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).

Breathlessness and looking pale

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

Sore mouth and lips

Mouth sores and ulcers, and sore lips can be painful. Keep your mouth and teeth clean; drink plenty of fluids; avoid acidic foods such as oranges and lemons; chew gum to keep the mouth moist and tell your doctor or nurse if your mouth is sore. 

Bleeding in different parts of your body 

You might have bleeding in different parts of your body. This can sometimes be heavy. For example, you might have bleeding in your digestive system . If you are sick (vomiting), you might notice some blood. 

Less commonly you might see blood in your poo which may be heavy. These symptoms can also make you feel dizzy and very tired.

Heavy bleeding can be life threatening. Call your hospital advice line straight away if you have symptoms or any unusual bleeding.  

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.

Inflammation of the digestive system

You might have inflammation and pain in the digestive system. Including your throat, food pipe (oesophagus), and tummy (stomach). You may find it painful to swallow drinks or food and have heartburn . 

You can also have inflammation of the back passage (rectum) that can cause diarrhoea. Other symptoms are pain, bleeding, and discharge from the rectum.

Speak to your doctor, pharmacist, or nurse if you have any of these symptoms, they will tell you what you can take to relieve the symptoms.

Diarrhoea

Contact your advice line if you have diarrhoea. For example, in one day you have 2 or more loose bowel movements than usual. If you have a stoma , you might have more output than normal. Your doctor may give you anti diarrhoea medicine to take home with you after treatment.

Try to eat small meals and snacks regularly. It’s best to try to have a healthy balanced diet if you can. You don’t necessarily need to stop eating foods that contain fibre. But if your diet is normally very high in fibre, it might help to cut back on high fibre foods such as beans, nuts, seeds, dried fruit, bran and raw vegetables. 

Drink plenty to try and replace the fluid lost. Aim for 8 to 10 glasses per day.

Difficulty breathing

You may have difficulty breathing with wheezing and coughing. Let your healthcare team know straight away if this happens. 

Acute cholinergic syndrome

Irinotecan can cause some people to develop a set of side effects during or within the first 24 hours after having the drug. These side effects include diarrhoea which may be severe. Other symptoms include sweating, stomach cramps, increased production of saliva, and watery eyes. You may have an injection of atropine before the irinotecan to reduce these side effects.

Changes to your heart 

These drugs can cause changes to your heart rhythm. So before you start treatment you might have tests to check your heart, such as an electrocardiogram (ECG).

Less commonly you may have chest pain. Rarely it might cause a heart attack. You might also have problems with your heart pumping blood around the body properly. You can feel breathless, tired and weak, have swelling in your hands and feet, and feel generally unwell, this is also rare.

Changes to your blood pressure

During treatment, your blood pressure may be higher than normal. You might feel dizzy and have headaches, nosebleeds, blurred or double vision, or shortness of breath. You might also have low blood pressure, but this is less common. Symptoms include feeling lightheaded and dizzy.

Tell your nurse if you have any of these symptoms.

 Loss of appetite and weight loss

You might not feel like eating and may lose weight. Eating several small meals and snacks throughout the day can be easier to manage. You can talk to a dietitian if you are concerned about your appetite or weight loss.

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. 

Dehydration

Dehydration means there isn't enough fluid in your body. You might find you aren't passing much urine and the colour is a very dark yellow. Your skin might be very dry and you might feel dizzy. So make sure you drink around 2 litres of fluid every day. Tell your nurse or doctor if you are not able to drink this much. 

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.

Slow wound healing

Any wounds you might have can take longer to heal. Keep wounds clean to prevent infection. Contact your GP or specialist nurse if you are worried about a wound.

Tiredness and weakness

Tiredness and weakness (fatigue) can happen during and after treatment. Doing gentle exercises each day can keep your energy up. Don't push yourself, rest when you start to feel tired and ask others for help.

Headaches

Let your doctor or nurse know if you have headaches. They can give you painkillers such as paracetamol to help.

Changes in your voice

You may notice that your voice sounds different. This is sometimes called a hoarse voice. Speak to your healthcare team if you are worried about this.

Problems with your kidneys

This treatment can affect your kidneys . Protein in your pee (urine) is an early sign. Your nurse will check your urine for protein before each course of treatment. Or they might ask you to provide a 24-hour urine collection. They will tell you more about this if you need to have this test. If you have protein in your pee your doctor may stop your treatment until it improves.

Rarely you might have a condition that causes the kidney to leak fluid into the tissues. This can cause swelling around the body.

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. You have regular blood tests to check for any changes in the way your liver is working.

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:

• a serious reaction to an infection called sepsis - symptoms can include feeling very unwell, not passing urine, slurred speech or confusion, breathlessness, mottled or discoloured skin, extreme shivering or muscle pain. Call 999 or go to your local Accident and Emergency (A&E) immediately if you have any of these symptoms
• constipation
• high temperature (fever)
• symptoms of having a cold. You may feel achy and tired, have a blocked nose, with sneezing and coughing
• a runny nose without having a cold
• abnormal opening between two internal parts of the body (fistula)
• swollen veins in the back passage that feel like small lumps (known as piles or haemorrhoids)
• pain in your back passage (rectum) that comes and goes
• toothache
• changes in the colour of the skin. Rarely you might have other skin problems such as rash, dry, red inflamed and itchy skin. You might have an increased sensitivity to sunlight
• an allergic reaction - symptoms include difficulty breathing, dizziness or general swelling of your hands, face, throat or a skin reaction including hives. Let your nurse know straight away if this happens
• inflammation of the veins
• blood clots that are life threatening- signs are pain, swelling and redness where the clot is. Feeling breathless can be a sign of a blood clot on the lung. Contact your advice line straight away if you have any of these symptoms
• an infection in your pee (urinary tract infection). Symptoms include peeing more often, pain or discomfort when you have a pee and it might smell bad or look cloudy

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:

• feeling very sleepy

• feeling confused and disorientated, and having problems with walking or speaking

• rarely you might have a condition where tiny blood clots develop in the small blood vessels. This is more likely to happen in the blood vessels of the kidneys and brain

• eye problems including eyes moving quickly from side to side (nystagmus), swollen eyes, watery eyes, blocked tear ducts, and your eyes can be sensitive to light

• shaking and trembling

• stiffness and slow movement

• feeling weak

• muscle twitching or feeling rigid

• an increase in the muscle tone of your legs and feet causing them to be stiff

• nail problems such as thickening, inflammation, pain, changes in the colour of the nail and nail bed

• feeling dizzy

• raised levels of ammonia in the blood - symptoms include feeling irritable, fits (seizures), and problems with coordination and speech

• changes in the brain that are usually reversible, causing a sudden onset of symptoms including headaches, dizziness, confusion, fits and changes to your vision

• lack of blood supply to the brain, gastric organs and your arms, legs, fingers and toes

• a hole developing in the digestive tract. This could be the food pipe, stomach, bowel and back passage. Symptoms include tummy pain, feeling or being sick, and a high temperature. Call your healthcare team straight away of you have these symptoms

• damage to the bone in the jaw, you might have pain or swelling in your mouth or loose teeth

Other side effects

If you have side effects that aren't listed on this page, you can look at the FOLFIRI and individual drug pages:

• fluorouracil (5FU)
• irinotecan
• FOLFIRI

What else do you need to know?

Other medicines, food and drink

Cancer drugs can interact with medicines, herbal products, and some food and drinks. We are unable to list all the possible interactions that may happen. An example is grapefruit or grapefruit juice which can increase the side effects of certain drugs.

Tell your healthcare team about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies. Also let them know about any other medical conditions or allergies you may have.

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.    

Pregnancy and contraception

This drug may harm a baby developing in the womb. It is important not to become pregnant while you are having treatment with this drug and for at least 6 months afterwards.

Men having treatment with this drug are advised not to get someone pregnant during treatment and for 3 months after stopping treatment.

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 you're having treatment.

Breastfeeding

It is not known whether these drugs come through into the breast milk. Doctors usually advise that you don’t breastfeed during this treatment.

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

For further information about each drug and the possible side effects go to the electronic Medicines Compendium (eMC) website. You can find patient information leaflets for each drug 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.