E-CMF (Epi-CMF)

E-CMF is the name of a combination of chemotherapy drugs used to treat breast cancer. It is also sometimes called Epi-CMF and is made up of the drugs

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

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

The side effects of a combination of drugs are usually a mixture of those of each drug. You may get some or all of the side effects. The combination may increase or decrease your chance of getting each side effect, or it may change its severity. The side effects associated with E-CMF are listed below. You can use the underlined links to find out more about each one. For more information, see our cancer drug side effects section.

You usually have chemotherapy as cycles of treatment. E-CMF is usually 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. So 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. You have them put in just before your course of treatment starts and they stay in as long as you need them.

Epirubicin is a red fluid. Methotrexate is a clear yellow fluid. Cyclophosphamide and 5FU are colourless fluids. You may have cyclophosphamide as tablets. You swallow the tablets with water, ideally on an empty stomach.

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 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 day 1 of your cycle and again on day 8. You then have a break for 3 weeks. This completes one cycle (4 weeks). You repeat this cycle 4 times over 4 months.

If you are having cyclophosphamide tablets, you have the epirubicin in the same way as above – every 3 weeks for 12 weeks. Then you have 4 cycles of CMF. From day 1 of your cycle, you take cyclophosphamide tablets daily for 14 days (2 weeks). On day 1 you also have methotrexate and 5FU injections. On day 8 (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.

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

Temporary drop in the number of blood cells made by the bone marrow, causing

• 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, sore throat, pain passing urine or feel cold and shivery
• 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)

Some of these side effects can be life threatening, particularly infections. You should contact your doctor if you have any of these effects. Your doctor will check your blood counts regularly to see how well your bone marrow is working.

Other common side effects include

• 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 drugs 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 is treated with epirubicin has complete head and body hair loss but the hair grows back after the treatment ends
• Diarrhoea - it is important to drink plenty of fluid and tell your doctor 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
• Blurred vision or watery eyes
• Changes to the heart muscles can occur with epirubicin – it can cause temporary heart rhythm changes but this usually goes back to normal after treatment ends - your heart will be checked before you start treatment
• Your urine may turn pink or red for a day or so after treatment with epirubicin - it is nothing to worry about
• Epirubicin can cause 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 remember to cover up or use sun block on exposed skin
• Women may stop having periods (amenorrhoea) during treatment and for a while afterwards
• E-CMF may have a harmful effect on a developing baby, so talk to your doctor about contraception before having treatment if there is any chance that you or your partner could become pregnant
• Loss of fertility - you may not be able to get pregnant or father a child after treatment with this drug so if this is important for you, talk to your doctor about fertility before starting treatment

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

• Inflammation around the drip site – if you notice any signs of redness, swelling or leaking at your drip site, tell your doctor or chemotherapy nurse immediately
• Epirubicin and methotrexate can cause an allergic reaction – tell your nurse if you have sudden skin rashes and itching, a temperature, shivering, redness of the face, feeling of dizziness, headaches, breathlessness, anxiety or you urgently want 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

Fewer than 1 in 100 people have these.

• Heart problems due to fluorouracil and epirubicin – there is a very small risk of permanent damage to the heart that could lead to angina or a heart attack
• Fluid retention with cyclophosphamide – let your doctor or nurse know if you get swollen ankles
• Cyclophosphamide can cause 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 caused by fluorouracil
• There is a small risk of developing another cancer years after finishing treatment with cyclophosphamide and epirubicin

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

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

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

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 and yellow fever. 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 for you to be in contact with other people who've had live vaccines as injections. There can be problems with oral vaccines, but not many people in the UK have oral vaccines 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.