Fludarabine, cyclophosphamide and rituximab (FCR)

FCR is a combination of cancer drugs used to treat chronic lymphocytic leukaemia (CLL). It includes the drugs we list below, next to each drug we have how you pronounce it in brackets:

• fludarabine (flu-dara-bin)

• cyclophosphamide (sike-low-foss-fa-mide)

• rituximab (ri-tuk-si-mab)

Fludarabine and cyclophosphamide are chemotherapy drugs. Rituximab is a type of targeted cancer drug called a monoclonal antibody .

How does FCR work?

These cancer drugs destroy quickly dividing cells, such as cancer cells.

How do you have FCR?

You usually have FCR as a combination of tablets and a drip into your bloodstream (intravenously). Or you may have all the drugs as a drip into your bloodstream. 

Into your blood stream

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.

Taking your tablets

Whether you have a full or empty stomach can affect how much of a drug gets into your bloodstream.

You should take the right dose, not more or less.

Talk to your healthcare team before you stop taking a cancer drug, or if you have missed a dose.

How often do you have FCR?

You usually have FCR as cycles of treatment . Each cycle of treatment lasts 4 weeks. You have treatment either:

• for the first 3 days of week 1 and then not have treatment for 25 days or
• for the first 5 days of week 1 and then not have treatment for 23 days

 This is to allow your body to recover.

Depending on your needs you may have up to 6 cycles, taking about 6 months in total. 

You have each cycle of treatment in the following way:

Then your next cycle of treatment starts. 

You might have fludarabine and cyclophosphamide for 5 days. 

For the first cycle of treatment your dose of rituximab might be split over 2 days. 

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 have a blood test to check for viruses such as hepatitis B, hepatitis C, HIV or cytomegalovirus (CMV) . This is called a viral screen. You may not know if you have one or more of these viruses. But it is important for your doctor to know as this treatment can weaken your immune system .

What are the side effects of FCR?

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. 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:

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 and bleeding

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).

Reactions during or after having rituximab

This can happen while having rituximab or within the next 24 hours. These include:

• flu-like symptoms (high temperature, chills, muscle aches, tiredness, dizziness and headache)
• low blood pressure
• flushing
• allergic reactions such as skin rashes, itching, feeling of swelling in the tongue or throat, irritation of the nasal passages, wheezing, coughing and breathlessness 

They are most noticeable when you have your first treatment of rituximab. You will have medications beforehand to try and prevent a reaction. 

General swelling

This most often affects the:

• hands
• feet
• area around the eyes
• lips and tongue
• genitals

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.

Skin problems

Skin problems include a skin rash, dry skin and itching. This usually goes back to normal when your treatment finishes. Your healthcare team can tell you what products you can use on your skin to help.

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. 

Fever or chills

You might have a high temperature (fever). Or you might feel cold and shiver (chills). Tell your doctor or nurse they might be able to prescribe medication for this. 

Headaches

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

Low levels of an antibody called immunoglobulin G in your body

Immunoglobulin G is an antibody made by the immune system to fight bacteria and viruses. You have regular blood tests during and after treatment to check for this.

Cough

Tell your doctor or nurse if you have a cough.

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.

Inflammation of the bladder

You might have pain when you pass urine. Or you may see blood when you pass urine. This is caused by inflammation of the bladder. Let your doctor know if this happens. 

You should drink 8 to 12 cups of fluid a day to try to prevent this.

Feeling tired and lacking energy (fatigue)

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.

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 high level of sugar (glucose)

• inflammation or infection that severely affects the body’s organs. Signs include fainting, tiredness, weakness, sleepiness, breathing fast and shallow, changes to heartbeat, feeling sick, fever and chills. Contact the advice line or the healthcare team.

• loss of appetite and weight loss

• changes to your sense of touch such as reduced sense of touch, tingling and numbness (pins and needles)

• feeling anxious, nervous or troubled (agitated)

• feeling dizzy

• high blood pressure or low blood pressure

• trouble sleeping

• eye problems such as watery eyes, itchy and red eyes (conjunctivitis) or changes to your eyesight (vision)

• ear pain and ringing in the ears (tinnitus)

• heart problems such as changes to how fast your heart beats, the rhythm and heart attack

• chest pain and shortness of breath

• runny nose

• difficulty swallowing and sore throat

• indigestion

• a low level of calcium and an enzyme called LDH in your blood

• sore, inflamed mouth, nose and throat

• constipation

• sweating and night sweats

• stiff, sore muscles and joints

• pain in the back, neck, tummy (abdomen) or where the cancer is

• cold syndrome. This is a reaction to cold temperatures causing fever, skin rash and joint pain can last from a few minutes to over an hour. Talk to your doctor or nurse if this happens

• another cancer. Talk to your doctor if you are concerned about this.

• changes to how well your liver works

• if you have had hepatitis B before it could come back

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:

• changes to 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. You usually have medication to take with the first cycle to lower the risk of tumour lysis syndrome.

• an allergic reaction that can cause a rash, shortness of breath, redness or swelling of the face and dizziness. Some allergic reactions can be life threatening, alert your nurse or doctor if notice any of these symptoms.

• pain at the infusion site

• enlarged lymph glands

• depression

• changes to how food and drink tastes

• confusion

• swollen tummy (abdomen)

• lung problems such as inflammation, asthma and difficulty breathing

• changes to hearing including deafness

• changes to how your pancreas works

• low levels of the female sex hormones

• a condition where the immune system attacks the body. This is an autoimmune disorder such as Evan’s syndrome.

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?

Having blood transfusions after fludarabine

If you are having, or have had, fludarabine treatment you must always receive specially treated (irradiated) blood if you need a transfusion. This is to prevent a side effect called graft versus host disease . If you need to have a blood transfusion, check with your doctor or nurse that the blood has been irradiated.

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.    

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 are having treatment. Women must not become pregnant for at least a year after the end of treatment. Men should not get someone pregnant for at least 6 months after 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 having treatment.

Breastfeeding

Don’t breastfeed during this treatment and for 12 months afterwards. The drug may come through in the 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.

Immunisation

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.