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This page tells you about the chemotherapy drug combination CMF and its possible side effects. There is information about


What CMF is

CMF is the name of a chemotherapy combination used to treat breast cancer. Doctors most often use it to try to stop breast cancer from coming back after surgery and radiotherapy. This is called adjuvant therapy. CMF is

  • C = Cyclophosphamide
  • M = Methotrexate
  • F = Fluorouracil (5FU)

You can click on the links above to find out about the side effects of each individual drug.


How you have CMF treatment

In the UK, it is most common to have CMF as injections and tablets. You have each treatment over 3 or 4 weeks as cycles of treatment. You take cyclophosphamide tablets every day for the first 2 weeks and have injections of methotrexate and 5FU on the 1st day of the treatment cycle and then a week later. 

It is very important that you take tablets according to the instructions your doctor or pharmacist gives you. For example, 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. And never stop taking a cancer drug without talking to your specialist first. Keep tablets in tightly closed containers and out of the reach of children. Return any unused tablets to the pharmacy.

Instead of having CMF as described above you may have all the drugs by injection every 3 or 4 weeks. All 3 drugs are injected on the 1st day of each 3 or 4 week cycle and then you have them again a week later.

You usually have 4 to 6 cycles of CMF. CMF is often given as E-CMF where you have 4 cycles of epirubicin and then 4 cycles of CMF. 

The side effects associated with CMF are listed below. Use the links (underlined) to find out more about each side effect. Where there is no link please see our cancer drug side effects section, or use the search box at the top of the page.


Common side effects

More than 10 in every 100 people have one or more of the side effects listed below.

  • An increased risk of getting an infection from a drop in white blood cells – it is harder to fight infections and you can become very ill. You may have headaches, aching muscles, a cough, a sore throat, pain passing urine, or you may feel cold and shivery. If you have a severe infection this can be life threatening. Contact your treatment centre straight away if you have any of these effects or if your temperature goes above 38°C. You will have regular blood tests to check your blood cell levels
  • Tiredness and breathlessness due to a drop in red blood cells (anaemia) – you may need a blood transfusion
  • Bruising more easily due to a drop in platelets – you may have nosebleeds, bleeding gums after brushing your teeth, or lots of tiny red spots or bruises on your arms or legs (known as petechia)
  • Tiredness and weakness (fatigue) during and after treatment – most people find their energy levels are back to normal from 6 months to a year after their treatment finishes
  • Feeling or being sick – this can be a problem for some people taking cyclophosphamide tablets. Try taking anti sickness medicines at least an hour before you take your cyclophosphamide
  • Loss of appetite
  • Hair loss or thinning – some women only have mild thinning but others have more and some may have complete hair loss
  • Diarrhoea – drink plenty of fluids if you have diarrhoea. Let your nurse of doctor know if it is severe or continues for more than 3 days
  • A sore mouth or mouth ulcers 
  • Metallic taste or loss of taste – this may only be on the days when you are having your drugs. It should get better when your treatment finishes
  • Sore eyes – they may feel as if they have grit in them
  • Blurred vision or watery eyes
  • Women may stop having periods (amenorrhoea) but this may only be temporary
  • Loss of fertility – you may not be able to become pregnant or father a child after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future. Men may be able to store sperm before starting treatment

Occasional side effects

Between 1 and 10 in every 100 people have one or more of these.

  • Skin changes – your skin may darken or you may have an itchy rash
  • Your skin may become sensitive to sunlight so use a high factor sun cream and cover up when you go out
  • Nail changes – your nails may become ridged, or darken. They may become brittle and chip or break easily
  • Coughing or breathlessness
  • Liver changes that are very mild and unlikely to cause symptoms – the liver will almost certainly go back to normal when the treatment ends. You will have regular blood tests to check how well your liver is working
  • Kidney changes that are mild and unlikely to cause symptoms may occur – they will almost certainly go back to normal when treatment finishes. You will have regular blood tests to check how well your kidneys are working

Rare side effects

Fewer than 1 in 100 people have these effects.

  • An allergic reaction when you are having methotrexate can cause an itchy rash, a high temperature and shivering, redness of the face, dizziness, a headache or breathlessness. Tell your chemotherapy nurse straight away if you have any of these symptoms
  • Burning, stinging or pain on passing urine (cystitis) – if you see blood in your urine contact your nurse or doctor straight away
  • Heart problems – there is a very small risk of angina (chest pain) or a heart attack
  • Fluid build up causing swollen hands and feet
  • Confusion or unsteadiness
  • There is a small risk of developing another cancer years after finishing the treatment

Important points to remember

The side effects above may be mild or more severe. A side effect may get better or worse through your course of treatment, or more side effects may develop as the course goes on. This depends on

  • How many times you've had the drug before
  • Your general health
  • The amount of the drug you have (the dose)
  • Other drugs you are having

Coping with side effects

Talk to your doctor, pharmacist or nurse about all your side effects so they can help you manage them. They can give you advice or reassure you. Your nurse will give you a contact number to ring if you have any questions or problems. If in doubt, call them.

Other medicines

Tell your doctor about any other medicines you are taking, including vitamins, herbal supplements and over the counter remedies. Some drugs can react together.

Pregnancy and contraception

These drugs may harm a baby developing in the womb. It is important not to become pregnant or father a child while you are having treatment and for a few months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment.


Do not breastfeed during this treatment because the drugs may come through in the breast milk.


Immunisations and chemotherapy

You should not have immunisations with live vaccines while you are having chemotherapy or for at least 6 months afterwards. In the UK, these include rubella, mumps, measles (usually given together as MMR), BCG, yellow fever and Zostavax (shingles vaccine).

You can have other vaccines, but they may not give you as much protection as usual until your immune system has fully recovered from your chemotherapy. It is safe to have the flu vaccine.

It is safe for you to be in contact with other people who've had live vaccines as injections. There can be problems with vaccines you take by mouth (oral vaccines), but not many people in the UK have these now. So there is usually no problem in being with any baby or child who has recently had any vaccination in the UK. You might need to make sure that you aren't in contact with anyone who has had oral polio, cholera or typhoid vaccination recently, particularly if you live abroad.


Related information


More information about CMF

This page does not list all the very rare side effects of this treatment that are very unlikely to affect you. For further information look at the Electronic Medicines Compendium website at

If you have a side effect not mentioned here that you think may be due to this treatment you can report it to the Medicines Health and Regulatory Authority (MHRA) at

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Updated: 23 October 2014