FLAG

FLAG is the name of a cancer drug combination. It includes the drugs below. How to pronounce the drug names are in the brackets.

• FL - fludarabine (flu-dara-bin)
• A - Ara C but also known as cytarabine (sye-ta-ra-bin)
• G - granulocyte colony stimulating factor (G-CSF)

It is a treatment for acute leukaemia.

How does FLAG work?

Cytarabine and fludarabine are a type of chemotherapy drug called an antimetabolite . Antimetabolites kill cancer cells by stopping them from making and repairing DNA  that they need to grow and multiply.

G-CSF is a type of growth factor. Growth factors are proteins made naturally in the body. One of the things they do is make the bone marrow  produce blood cells . G-CSF is a man made (synthetic) version of these proteins. It’s a type of growth factor that makes the bone marrow produce more white blood cells. This can reduce the risk of infection after FLAG treatment.

How do you have FLAG?

You have fludarabine and cytarabine as a drip into your bloodstream (intravenously). You have G-CSF as an injection under the skin.

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

If you don't have a central line

You might have treatment through a thin short tube (a cannula) that goes into a vein in your arm. You have a new cannula each time you have treatment.

Risk of tissue damage

When you are having this treatment through a cannula it could damage the tissue if it leaks out of the vein. This is called extravasation. This can happen anywhere along the vein that the drug is going into. It doesn’t happen very often. Tell your nurse straight away if you notice any changes such as swelling, redness, pain, burning, or a stinging feeling.

Your nurse will stop the drug treatment. And they will treat the area to relieve symptoms and reduce tissue damage. Contact your healthcare team if you develop any of these symptoms when you are at home.

Medicine you have as an injection under your skin

You usually have injections under the skin (subcutaneous injection) into the stomach, thigh or top of your arm.

You might have stinging or a dull ache for a short time after this type of injection, but they don't usually hurt much. The skin in the area may go red and itchy for a while.

When do you have FLAG?

You usually have FLAG as a course of several cycles of treatment. A cycle of treatment means that you have these drugs and then have a rest to allow your body to recover.

Each cycle of treatment lasts about 28 days (4 weeks). You may start your next cycle the following day. Or you may need to wait until your blood counts have recovered. This can vary from person to person.

You might have up to 2 cycles of FLAG. You have each cycle of treatment in the following way: 

Once your blood count has recovered you start your second cycle of FLAG.

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 treatment starts you may have a blood test to check for viruses such as hepatitis B, hepatitis C, and HIV . This is called a viral screen.

It’s important for your doctor to know if you have had any of these viruses. This is because this treatment can weaken your immune system and can cause the virus to become active again (reactivation). 

What are the side effects of FLAG?

Side effects can vary from person to person. They also depend on what other treatments you're having. 

When to contact your team

Your doctor, nurse or pharmacist will go through the possible side effects. They will monitor you 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

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 getting an 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. 

A serious reaction to an infection (sepsis)

Sepsis happens when your body has an overwhelming response to an infection. Symptoms include:

• Slurred speech or confusion
• Extreme shivering or muscle pain
• Passing no urine (in a day)
• Severe breathlessness
• It feels like you’re going to die  
• Skin mottled or discoloured

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 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).

Lung problems

This treatment can commonly cause lung problems such as a cough, breathlessness, or taking shallow breaths. This could be due to an infection, such as pneumonia or fluid in your lungs, stopping them from expanding fully.

Some people might have symptoms that include fast and shallow breathing, tiredness, drowsiness, confusion, feeling like you will faint and shortness of breath. This is called acute respiratory distress syndrome (ARDS). It causes a lack of oxygen to your organs such as the lungs, heart and brain. 

Other less common lung problems include changes to the lung tissue, making it less flexible or inflammation of the lungs (pneumonitis), or you might have scarring (pulmonary fibrosis).

Sore mouth

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.

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.

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.

Pain in your tummy (abdominal), bones or muscles

You might experience pain in your tummy, bones or muscles. Speak to your doctor as they can prescribe medicine to help. 

Inflammation and ulcers of the opening at the end of the bowel (anus)

Talk to the team looking after you about this. They might be able to give you medicines or creams to help with this.

Liver changes

You might have liver changes that are usually mild, your doctor may feel that your liver is swollen. This usually goes back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working.

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. 

Skin changes

You might notice skin changes, such as dryness, itching, freckles and rashes similar to acne on your face, neck and trunk. 

Occasionally you may have other symptoms such as peeling of the skin or ulcers.

Very rarely this treatment can cause a severe skin reaction that may start as tender red patches which leads to peeling or blistering of the skin. You might also feel feverish and your eyes may be more sensitive to light. This is serious and could be life threatening.

Tell your healthcare team if you have any skin changes. They might be able to prescribe medicine or advise on creams and lotions to use.

High temperature (fever)

If you get a high temperature, let your healthcare team know straight away. 

Cytarabine syndrome

Cytarabine syndrome sometimes happens about 6 to 12 hours after having this drug. 

It causes a combination of symptoms. These include a high temperature, aching muscles, bone pain, occasionally chest pain, a rash, sore eyes, and extreme weakness. Steroids can help to prevent or treat this syndrome.

Biopsy and blood test results

Cytarabine can cause abnormal results. Your doctor or nurse might need to take more biopsies or blood tests. Your healthcare team can explain this to you more.

Sleeping problems

You might feel very tired or find you are falling asleep during the day. Do not drive or operate machinery if you feel very sleepy.

Occasionally you may have problems getting to sleep or staying asleep (insomnia).

Let your doctor know straight away if you are very sleepy. 

Difficulty with movement and speech

You might have problems with your movement and speech. This might be because of weakness in the muscles used for speech. You might be unsteady when you stand and find it difficult to walk. You might lose muscle control causing coordination problems.

Tiredness and weakness (fatigue)

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.

Eye changes 

You might have eye problems including eye pain, blurred vision, loss of vision, sore, red, itchy, dry eyes (conjunctivitis) or an infection.

You have steroid eye drops to try and prevent conjunctivitis during treatment with high dose cytarabine. Your healthcare team can explain more.

Tell your healthcare team if you have any eye problems.

Headaches

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

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:

• blood cancers such as myelodysplastic syndrome
• loss of appetite
• numbness or tingling in fingers or toes (peripheral neuropathy)
• fluid build up in different parts of the body (oedema)
• generally feeling unwell
• inflammation and decreased blood supply to the bowel, this can be very serious. Symptoms might include passing blood from your bottom, feeling or being sick, constipation, diarrhoea or swelling of your tummy
• enlarged spleen  - this might cause tummy pain
• high levels of an enzyme  in your blood that can be a sign of injury to your body’s tissues – you have regular blood tests to check this
• feeling dizzy
• high or low blood pressure – you might have headaches or feel faint
• loss of sensation or touch causing tingling and numbness
• muscle spasms
• pain or difficulty passing urine
• chest pain
• a reaction to G-CSF – you might get a rash, shortness of breath, redness or swelling of the face and dizziness – some reactions can be life threatening, alert your nurse or doctor if notice any of these symptoms

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:

• a disorder where the body attacks its own blood cells (an autoimmune disorder) such as autoimmune haemolytic anaemia, acquired haemophilia, or pemphigus

• changes to the levels of chemicals in your blood due to the breakdown of tumour cells (tumour lysis syndrome) - you have regular blood tests to check for this

• feeling confused

• abnormal levels of pancreatic enzymes that are usually picked up in blood tests

• bleeding in your stomach or gut, symptoms include passing black or tarry poo, stomach cramps, being sick (vomiting) blood, dark or bright red blood in your poo, looking pale, or feeling faint

• being in a coma, this means that you cannot be woken

• fits (seizures)

• heart problems such as irregular heartbeat or heart failure. Symptoms of heart failure include breathlessness, tired, weakness, swelling in your legs and ankles, feeling faint or lightheaded

• skin cancer

• high uric acid levels in the blood that may cause gout – you have regular blood tests to check this

• thinning of the bones which can make the bones weaker and easier to break (osteoporosis)

• leaking of fluid and proteins out of the blood vessels into the tissues (capillary leak syndrome)

• plum coloured, raised, painful sores on your legs or arms and sometimes the face and neck with a high temperature (Sweets syndrome)

Other side effects

There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include:

• an allergic reaction which might lead to swelling in areas such as the hands, feet, lips, tongue, around the eyes or genitals (allergic oedema)

• long term disease of the heart muscle (cardiomyopathy) - this can be life threatening

• personality changes

• inflammation of your pancreas – symptoms include severe tummy pain, feeling or being sick, a high temperature or you may have loose poo

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do you need to know?

Other medicines, foods 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.

Having blood after this treatment

After having this treatment you should only have blood or platelets that are first treated with radiation (irradiated). The radiation lowers the risk of a reaction between your blood cells and the cells in the transfusion. No harm comes from having the irradiated blood.

In your medical records there is a note saying you should only have irradiated blood. You have a card to carry with this information. This is in case you need treatment at another hospital.

Pregnancy and contraception

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. 

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.    

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.

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.