Doxorubicin and ifosfamide

Doxorubicin and ifosfamide is a chemotherapy drug combination. Your pronounce these drugs names as:

• doks-oh-roo-bi-sin
• eye-foss-fa-mide

They are a treatment for soft tissue sarcomas.

How does doxorubicin and ifosfamide work?

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

How do you have doxorubicin and ifosfamide?

You have doxorubicin and ifosfamide as a drip into your bloodstream (intravenously).

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

How often do you have doxorubicin and ifosfamide?

You have doxorubicin and ifosfamide as cycles of treatment. This means you have the drugs and then a rest to allow your body to recover.

Each cycle of treatment lasts 21 days (3 weeks). You usually have up to 6 cycles in total. Your doctor will discuss the length of your treatment with you.

The following is one way of having each cycle of treatment:

You then start the next cycle

Mesna and GCSF

You usually have ifosfamide with another drug called mesna. You have mesna either as a drip (infusion) into your bloodstream or as tablets.

Mesna is not a chemotherapy drug. It stops the ifosfamide from irritating your bladder and making the lining bleed.

You usually also have a medcine such as filgrastim or pegfilgrastion. Its a granulocyte colony stimulating factor (GCSF). This makes your bone marrow produce white blood cells more quickly after the chemotherapy. You need white blood cells to protect you against infections.

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.

You will also have tests such as an ECHO to check how well your heart works.

What are the side effects of doxorubicin and ifosfamide?

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. Talk to your healthcare team if you have any new symptoms that you think might be a side effect of your treatment.

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: 

Increased 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, cough, headaches, feeling cold and shivery, pain or burning feeling when weeing, or generally feeling 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. 

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).

Less commonly your body might develop bleeding from other areas of the body. Let your nurse or doctor know if you notice any bruising or are bleeding from anywhere.

Breathlessness

You might be breathless and look pale due to a drop in red blood cells. This is called anaemia.

High temperature or chills

You might get a high temperature. Or you might feel cold or start shivering (chills). 

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. 

Inflammation of your digestive system

Your digestive system includes the mouth, food pipe, stomach, bowel and the back passage (rectum).

This treatment can cause parts of your digestive system to be sore and painful. You might also have ulcers. This commonly starts in the mouth and may feel as though your mouth is burning. This can cause problems in you being able to drink and eat enough.

Other symptoms include diarrhoea, feeling sick and bleeding from your back passage.

You can have painkillers to lessen the pain. You will have mouthwashes to keep your mouth healthy. You may receive a gel for your back passage to help with soreness.

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.

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 changes

You might get a rash and your skin might be more sensitive to sunlight causing a reaction. It’s important to protect your skin. The best way is to find shade, cover up your skin and wear sunscreen.

The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome.

Less commonly you might develop a raised itchy rash or your skin may get itchy. Areas of skin may appear darker than usual. Your skin might change colour in areas where you had radiotherapy previously.

Nail changes

Your nails may become loose and come off. They may also get darker during treatment but this is less common.

Tiredness and weakness

You might feel very tired and as though you lack energy.

Various things can help you to reduce tiredness and cope with it, for example exercise. Some research has shown that taking gentle exercise can give you more energy. It is important to balance exercise with resting.

Heart changes

It’s very common to have changes to the heart muscle or rhythm that are picked up on an ECHO, ECG or both. Less commonly this treatment can cause the heart to become weak and damage the heart muscle.

You have heart tests to check how well your heart is working before you start treatment. You may also have them during and after treatment.

Heart changes can happen during treatment or some months and years after you have finished treatment.

Symptoms of heart changes can include shortness of breath, ankle swelling, chest pain, fast beating, fluttering or pounding heart.

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working.

Inflammation and irritation of the bladder

Ifosfamide can cause inflammation and bleeding of the bladder lining. This is called haemorrhagic cystitis. This can cause you to:

• pass urine more often than usual
• find it difficult to pass urine
• have a burning feeling or pain when you go
• not be able to wait when you need to go
• pass blood or blood clots 

It helps to drink plenty of fluids. You have a drug called mesna to help protect your bladder during treatment.

Tell your nurse or doctor straight away if you have any problems passing urine.

Kidney changes

You might have some changes in the way your kidneys work. You have regular blood tests to check how well they are working.

Kidney changes can include acute kidney failure. This means your kidneys stop working suddenly. Let your doctor or nurse know straight away if you have breathlessness, tiredness and swelling of the body due to fluid build up.

Red or pink urine

You might have red or pink urine. This won't harm you. It’s due to the colour of the chemotherapy and lasts for one or two days.

Blood clots

Blood clots can develop in the deep veins of your body, usually the leg. This is called deep vein thrombosis (DVT). A blood clot can be very serious if it travels to your lungs (pulmonary embolism), although this isn’t common.

Symptoms of a blood clot include:

•    pain, redness and swelling around the area where the clot is and may feel warm to touch
•    breathlessness
•    pain in your chest or upper back – dial 999 if you have chest pain
•    coughing up blood

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 serious reaction to an infection also known as sepsis. Signs can include feeling very unwell, not passing urine, being sick, a very high or very low temperature or shivering - contact your advice line straight away if you have any of these symptoms

• an eye infection (conjunctivitis) – your eyes may feel gritty, itchy, sticky from pus, watery and look red

• pain or burning feeling from the tummy (abdomen) and food pipe

• inflammation of a vein near the skins surface (phlebitis), causing pain and tenderness along the vein

• loss of appetite

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:

• low blood pressure that can cause you to feel lightheaded or dizzy

• a second cancer such as leukaemia or lymphoma

• loss of body fluid (dehydration)

• thickening and hardening of the wall of the veins (phlebosclerosis)

• 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 you notice any of these symptoms

Other side effects

There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include:

• small blood clots developing throughout the bloodstream, blocking small blood vessels (disseminated intravascular coagulation)

• changes to the levels of chemicals in your blood due to the breakdown of tumour cells (tumour lysis syndrome) – you will have regular blood tests to check this

• mental health changes such as not speaking, confusion, seeing things that are there, panic and anxiety

• scarring of the lungs or fluid building up in the lungs causing them not to get enough air. Less oxygen reaches the bloodstream causing breathing problems

• a severe skin reaction that may start as tender red patches which leads to peeling or blistering of the skin. You might also feel feverish and your eyes may be more sensitive to light. This is serious and could be life threatening

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?

Other medicines, foods 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.

Pregnancy and contraception

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 2 weeks after your last dose. This is because these drugs may come through into your breast milk.

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.    

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.

Immunisations

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

For further information about each drug and the possible side effects go to the electronic Medicines Compendium (eMC) website. You can find patient information leaflets for each drug 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.