E-CMF (Epi-CMF) | Cancer Research UK
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This page tells you about the chemotherapy drug combination E-CMF and its possible side effects. There is information about


What E-CMF is

E-CMF is sometimes called Epi-CMF. It is a combination of chemotherapy drugs that includes 

  • E (Epi) – Epirubicin
  • C – Cyclophosphamide
  • M – Methotrexate
  • F – Fluorouracil

The links above take you to information about the individual side effects of each of these drugs.

E-CMF is a treatment for breast cancer. 

The side effects associated with E-CMF are listed below. 


How you have E-CMF

You usually have chemotherapy as cycles of treatment. E-CMF is given in two parts. You first have 4 doses of epirubicin over 3 months. Then you have the other 3 drugs (CMF) over the next 4 months. The course of treatment takes about 7 months in total.

You may have all the E-CMF drugs into your bloodstream (intravenously). You can have them through a thin, short tube (a cannula) put into a vein in your arm each time you have treatment. Or you may have them through a central line, a portacath, or a PICC line. These lines are long, plastic tubes that give the drugs directly into a large vein in your chest. The tube can stay in place throughout the course of treatment.

Epirubicin is a red fluid. Methotrexate is a clear yellow fluid. Cyclophosphamide and 5FU are colourless fluids. You may have cyclophosphamide as tablets. 

There are two ways to have E-CMF chemotherapy, depending on whether you are having cyclophosphamide injections or tablets. Your doctor or nurse will explain which one you are having and why.

If you have all the drugs as injections

If you are having all the drugs as injections, you have treatment in the following way. 

Every 3 weeks, for 12 weeks, you have an injection of epirubicin. So you have 4 injections in total. This completes your 4 cycles of epirubicin. 

You then have the CMF part of the treatment. You have cyclophosphamide, methotrexate and 5FU injections on the first day of your cycle and again a week later. You then have a break for 3 weeks. This completes one cycle (4 weeks). 

You repeat the cycle 4 times over 4 months.

If you are having cyclophosphamide as tablets

If you have cyclophosphamide as tablets, you have the epirubicin every 3 weeks for 12 weeks. 

Then you have 4 cycles of CMF. From the first day of your cycle, you take cyclophosphamide tablets daily for 2 weeks. You swallow the tablets with water, ideally on an empty stomach. On the first day you also have methotrexate and 5FU injections. A week later you repeat these injections. After you finish your cyclophosphamide tablets you have a break with no drugs for 2 weeks. This completes one cycle of the CMF over 4 weeks. 

You repeat this cycle 4 times over 4 months.

It is very important that you take the 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.


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 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 petechia)
  • Tiredness and weakness (fatigue) during and after treatment – it can be severe for up to 1 in 4 people (25%). The fatigue may continue after treatment has finished, but most people find their energy levels are back to normal within 6 months to a year
  • Feeling or being sick is usually well controlled with anti sickness medicines but can be severe in about 1 in 6 people (about 16%)
  • A sore mouth or mouth ulcers
  • Loss of appetite
  • Hair loss – everyone who has epirubicin has complete head and body hair loss but the hair grows back after the treatment ends
  • Diarrhoeait is important to drink plenty of fluids and tell your doctor or nurse if diarrhoea becomes severe or continues for more than 3 days
  • Metallic taste or loss of taste – this may only happen on the days when you are having your drugs and should get better when your treatment finishes
  • Irritated or sore eyes – they may feel as if they have grit in them but eye drops can help
  • Changes to the heart muscles – this can cause temporary heart rhythm changes but usually goes back to normal after treatment ends. Your doctor will check your heart before you start treatment
  • Your urine may turn pink or red for a day or so after treatment with epirubicin but this won't harm you
  • Blurred vision or watery eyes
  • Skin changes, such as rashes (which may be itchy), skin darkening, sensitivity to light, and redness or soreness in areas treated with radiotherapy. Don’t sit out in the sun and do remember to cover up or use sun block on exposed skin
  • Women may stop having periods (amenorrhoea) during treatment and for a while afterwards
  • Loss of fertility – you may not be able to become pregnant after this treatment. Talk to your doctor before starting treatment if you think you may want to have a baby in the future

Occasional side effects

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

  • Inflammation around the drip siteif you notice any signs of redness, swelling or leaking at your drip site, tell your nurse straight away
  • Epirubicin and methotrexate can cause an allergic reaction – tell your nurse if you have sudden skin rashes and itching, a temperature, shivering, or redness of the face. Also tell them if you feel dizzy or have headaches, breathlessness, anxiety, or a sudden need to pass urine
  • Your nails may become darker, brittle, or develop white lines
  • Changes to how your liver or kidneys work – you will have regular blood tests to check this

Rare side effects

Fewer than 1 in 100 people have these effects.

  • Heart problems – there is a very small risk of permanent damage to the heart that could lead to angina (chest pain) or a heart attack
  • Fluid build up – let your nurse know if you get swollen ankles
  • Changes in lung tissue that may lead to a cough or breathlessness – let your doctor or nurse know if you have this
  • Confusion or unsteadiness
  • There is a small risk of developing another cancer years after finishing treatment

Important points to remember

You may have a few of the side effects mentioned on this page. They may be mild or more severe. A side effect may get better or worse through your course of treatment. Or you may have more side effects 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)
  • How you have the drugs
  • 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 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

On this website you can read about





breast cancer

For more information, see our cancer drug side effects section


More information about E-CMF drugs

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

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 www.mhra.gov.uk.

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Updated: 31 December 2014