This information is about a chemotherapy treatment for chronic lymphocytic leukaemia (CLL) called FCR. It describes the drugs used, how they are given and some of the possible side effects. It should ideally be read with our general information about chemotherapy and CLL.
The drugs that are used
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FCR is named after the initials of the drugs used, which are:
Rituximab belongs to a group of drugs called monoclonal antibodies. Monoclonal antibodies can destroy some types of cancer cells while causing little harm to normal cells. They recognise certain proteins found on the surface of some cancer cells. The monoclonal antibody recognises the protein and locks on to it (like a key in a lock). This triggers the body’s immune system to attack the cancer cells and can sometimes cause the cells to destroy themselves.
Rituximab locks on to a protein called CD20, which is found on the surface of B-cell lymphocytes, one of the main types of normal white blood cells. CD20 is also present on the surface of the abnormal B-cell lymphocytes that occur in CLL. Rituximab attacks both abnormal (malignant) and normal B-cell lymphocytes. However, the body quickly replaces any normal white blood cells that are damaged, so the risk of side effects from this is small.
How treatment is given
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FCR can usually be given to you as a day patient. However, you might have to stay in hospital overnight for the first treatment. This is because the first dose of rituximab may be split into two parts, given over two days.
Before you start treatment you’ll need to have a blood test - either on the same day or a few days beforehand. You’ll also be seen by a doctor, specialist nurse or pharmacist. If the results of your blood test are normal, the pharmacy will prepare your treatment. All of this may take a couple of hours.
The nurse will then insert a thin, flexible tube (cannula) into a vein in your hand or arm. You may find this uncomfortable or a little painful, but it shouldn’t take long.
Once your treatment is ready, you’ll be given some anti-sickness (anti-emetic) drugs. These are usually given by injection through the cannula but can also be given as tablets.
The first dose of rituximab is given slowly into the vein as a drip (infusion) over a few hours. Your doctor may decide to divide the dose, so you have a smaller amount on day one and the rest given the next day. This is because some people can have an allergic reaction to rituximab. If you have a reaction, the infusion can be stopped and started again more slowly when the symptoms have reduced.
The chemotherapy drugs cyclophosphamide and fludarabine are usually taken as tablets. Cyclophosphamide tablets should be swallowed whole on an empty stomach. Fludarabine tablets should be swallowed whole with plenty of water. Occasionally, fludarabine and cyclophosphamide are given either by a slow injection or drip (infusion) through the cannula.
When all the drugs have been given the nurse will remove your cannula and you can go home.
You will be given a supply of anti-sickness tablets to take home with you. It’s important to take these regularly, as directed, even if you’re not feeling sick. This is because some anti-sickness drugs are much better at preventing sickness than stopping it once it starts.
How often treatment is given
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Your doctor may use the word ‘regimen’ (eg the FCR regimen) when talking about your chemotherapy. This means the whole plan or schedule of your particular treatment.
Usually you’ll have rituximab, as described, on day one of your treatment. You’ll also start a 5-day course of both chemotherapy tablets. You’ll then have a rest period for the next 23 days. This completes one cycle of your treatment.
If you’re having the treatment by injection, you’ll be given rituximab, cyclophosphamide and fludarabine on day one of your treatment. Further doses of cyclophosphamide and fludarabine are given on days two and three by slow injection or drip. For the next 25 days you’ll have a rest period with no treatment.
After the rest period you’ll start the next cycle of treatment. Each cycle lasts 28 days. Usually six cycles are given over six months. This makes up a course of treatment.
Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described here won’t affect everyone who is having FCR chemotherapy.
We have outlined the most common side but haven’t included those that are rare and unlikely to affect you. If you do notice any effects that aren’t listed here, discuss them with your doctor, chemotherapy nurse or pharmacist.
Some people have an allergic reaction to rituximab while it’s being given. Signs of this include flu-like symptoms (eg headache, fever or chills), feeling sick, skin rashes and itching, breathlessness, or pain in your back, tummy or chest.
It‘s most common with the first infusion, so the first dose is given slowly over a number of hours. You’ll also be given medicines before the treatment to help prevent or reduce any reaction. You’ll be monitored closely during your infusion but it's important to tell your nurse or doctor if you feel unwell or have any of the above symptoms. If you do have a reaction, it can be treated quickly.
Sometimes a reaction can happen a few hours after treatment. If you develop these symptoms or feel unwell after you get home, contact the hospital straight away for advice.
You may have a sudden feeling of warmth and some reddening in your face. This can happen for a short period of time while the drug is being given.
Low blood pressure
This may happen during the infusion of rituximab, so your blood pressure will be regularly checked.
If you usually take drugs to lower your blood pressure, your doctor may advise you to take these at least 12 hours before you have rituximab. It’s important not to do this without discussing it with your doctor first.
Risk of infection
Chemotherapy can reduce the number of white blood cells, which help fight infection. White blood cells are produced by the bone marrow. If the number of your white blood cells is low you will be more prone to infections. A low white blood cell count is called neutropenia.
Neutropenia can begin from three days after treatment and your resistance to infection may remain low for up to four weeks after the chemotherapy.
Your immune system may not recover completely for many months after the treatment has finished.
Contact your doctor or the hospital straight away if:
your temperature goes above 38°C (100.4°F)
you suddenly feel unwell, even with a normal temperature.
You will have regular blood tests to check the number of white blood cells in your blood. Occasionally it may be necessary to delay your treatment if the number of blood cells (blood count) is still low.
You may be given injections of G-CSF to help prevent the number of white blood cells getting too low. G-CSF is a type of protein that can stimulate the bone marrow to produce white blood cells. G-CSF is given as an injection under the skin (subcutaneously).
While taking fludarabine you are at risk of developing a chest infection called pneumocystis. To help prevent this you will be given an antibiotic called co-trimoxazole (Septrin®). You will need to take this during the fludarabine treatment and for a few months after treatment has finished.
Bruising or bleeding
FCR can reduce the production of platelets, which help the blood to clot. Tell your doctor if you have any unexplained bruising or bleeding, such as nosebleeds, bleeding gums, blood spots or rashes on the skin. You can have a platelet transfusion if your platelet count is low.
FCR can reduce the number of red blood cells, which carry oxygen around the body. A low red blood cell count is called anaemia. This may make you feel tired and breathless. Tell your doctor or nurse if you have these symptoms. You may need to have a blood transfusion if the number of red blood cells becomes too low.
Feeling sick (nausea) or being sick (vomiting)
This may begin soon after the treatment is given and can last for up to 24 hours. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent or greatly reduce nausea and vomiting. If the sickness isn't controlled, or if it continues, tell your doctor; they can prescribe other anti-sickness drugs that may be more effective.
Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.
Loss of appetite
Some people lose their appetite while they’re having chemotherapy. This can be mild and may only last a few days. If it doesn’t improve you can ask to see a dietitian or specialist nurse at your hospital. They can give you advice on improving your appetite and keeping to a healthy weight.
We have a slideshow with tips for coping with a poor appetite, which you might find helpful.
Feeling tired is a common side effect of chemotherapy, especially towards the end of treatment and for some weeks after it’s over. It’s important to try to pace yourself and get as much rest as you need. Try to balance this with some gentle exercise, such as short walks, which will help. If tiredness is making you feel sleepy, don’t drive or operate machinery.
You might like to watch our video of Denton's story of coping with fatigue.
Fever, chills and joint pain
These symptoms may occur from the time that the drug is given, but they do not usually last long. Your doctor may prescribe medicines to reduce these.
Less common side effects
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Treatment with FCR may cause changes in the way that your liver works, although it will return to normal when the treatment finishes. You're very unlikely to notice any problems but your doctor will take regular blood samples to check your liver is working properly.
Raised levels of uric acid in the blood. This can result in a condition called gout, which causes inflammation of the joints. To prevent this, you may be given a drug called allopurinol (Zyloric®) and you may be asked to drink plenty of fluids. While you are having FCR you will have regular blood tests to check your uric acid levels.
Sight changes, headaches, confusion, weakness and agitation These side effects are rare, but if they do occur, you should let your doctor know.
Hair thinning or loss
Hair loss is rare with this treatment, but your hair may become thinner. If you lose any hair it will grow back when the treatment has finished.
Your nurse can give you advice about coping with hair loss.
Your mouth may become sore or dry, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Some people may find sucking on ice soothing. Tell your nurse or doctor if you have any of these problems, as they can prescribe mouthwashes and medicine to prevent or clear mouth infections.
You may notice that food tastes different. Normal taste usually comes back after treatment finishes. A dietitian or specialist nurse at your hospital can give you advice about ways of coping with this side effect.
FCR can cause diarrhoea. This can usually be easily controlled with medicine but tell your doctor if it's severe or continues. It's important to drink plenty of fluids if you have diarrhoea.
Your nails may become darker or ridged. They usually return to normal within a few months of finishing the treatment.
Fludarabine can cause a rash or dry skin, which may be itchy. Your doctor can prescribe medicine to help with this. Cyclophosphamide may cause your skin to darken, but this is rare.
Changes to the lungs
The chemotherapy may cause some changes to the lungs. Tell your doctor if you smoke or if you notice any coughing or breathlessness.
Changes in the way your heart works This is very rare with standard doses, but may occasionally occur with high-dose treatment. The muscle of the heart may be affected, usually temporarily. Tests to see how well your heart is working may be carried out before the drug is given, and sometimes before each treatment.
It’s important to let your doctor know straight away if you feel unwell or have any severe side effects, even if they’re not mentioned above.
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Risk of developing a blood clot
Cancer can increase the risk of developing a blood clot (thrombosis), and chemotherapy may increase this risk further.
A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it’s important to tell your doctor straight away if you notice any of these symptoms. Most clots can be treated with drugs that thin the blood. The doctor or nurse can give you more information.
Some medicines, including those that you can buy in a shop or chemist, can be harmful to take when you are having chemotherapy. Tell your doctor about any medicines you are taking, including over-the-counter drugs, complementary therapies and herbal drugs.
Your ability to become pregnant or father a child may be affected by having this treatment. It's important to discuss fertility with your doctor before starting treatment.
Contraception It's not advisable to become pregnant or father a child while taking chemotherapy drugs, as it may harm the developing baby. It’s important to use effective contraception while taking this drug, and for at least a few months afterwards. You can discuss this with your doctor.
It’s not known whether chemotherapy drugs can be present in semen or vaginal fluids. To protect your partner it’s safest to either avoid sex or use a barrier form of contraception for about 48 hours after chemotherapy.
If you’re admitted to hospital for a reason not related to the cancer, it’s important to tell the doctors and nurses looking after you that you are having chemotherapy treatment. You should tell them the name of your cancer specialist so that they can ask for advice.
It’s a good idea to know who you should contact if you have any problems or troublesome side effects when you’re at home. Your chemotherapy nurse or doctor will give you details of who to contact for advice. This should include ‘out-of hours’ contact details if you need to call someone at evenings, overnight or at the weekend.
Anyone who has treatment with fludarabine should be given blood and platelet transfusions that have been treated with radiation (irradiated) for life. This lowers the risk of the donated blood cells reacting against your own. Your hospital team should give you a card to carry or a Medicalert to wear so that hospital staff are aware in case of an emergency.
Things to remember about chemotherapy tablets
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It’s important to take your tablets at the right times, as directed by your doctor.
Swallow your tablets whole with a glass of water.
Always tell any doctors treating you for non-cancerous conditions that you’re taking a course of chemotherapy tablets that should not be stopped or restarted without advice from your cancer specialist.
Keep the tablets in the original packaging and store them at room temperature, away from heat and direct sunlight.
Keep the tablets in a safe place, out of the reach of children.
If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Do not flush them down the toilet or throw them away.
If you are sick just after taking the tablets, tell your doctor as you may need to take another dose. Don't take another tablet without telling your doctor first.
If you forget to take a tablet, don’t take a double dose. Let your doctor know and keep to your regular dose schedule.
This fact sheet has been compiled using information from a number of reliable sources, including:
Sweetman, et al. Martindale: The Complete Drug Reference. 36th edition. 2009. Pharmaceutical Press.
British National Formulary. 60th edition. 2010. British Medical Association and Royal Pharmaceutical Society of Great Britain.
Perry MC. The Chemotherapy Source Book. 4th edition. 2007. Lippincott Williams and Wilkins.
Provan, et al. Oxford Handbook of Clinical Haematology. 3rd edition. 2009. Oxford University Press.
electronic Medicines Compendium (eMC). www.medicines.org.uk (accessed October 2011).