What is R-ICE?

R-ICE treatment is a combination of a targeted therapy and chemotherapy. It is named after the initials of the drugs used:

Rituximab is a targeted therapy drug. The others are chemotherapy drugs. Some people may have this treatment without rituximab. This treatment is called ICE.

Your cancer doctor will talk to you about this treatment and its possible side effects before you agree (consent) to have treatment.

It is best to read this information with our general information about targeted therapychemotherapy and the type of cancer you have.

More information about this treatment

This information is correct at time of publishing. But sometimes the types of cancer this treatment is used for, or treatment side effects, may change between revision dates.

You can talk to your cancer team if you want more detailed information about this treatment. Or visit the electronic Medicines Compendium (eMC) website, which has patient information leaflets (PIL) for individual drugs.

How R-ICE is given

You will be given ICE during a stay in hospital. Sometimes it may be given in a chemotherapy day unit. A chemotherapy nurse will give it to you.

During a course of treatment, you usually see a:

  • blood cancer doctor (haematologist)
  • chemotherapy nurse or a specialist nurse
  • specialist pharmacist.

This is who we mean when we mention doctor, nurse or pharmacist in this information.

Before or on the day of each treatment, a nurse or person trained to take blood (phlebotomist) will take a blood sample from you. This is to check that it is safe for you to have chemotherapy.

You will speak to a doctor, nurse or pharmacist before you have chemotherapy. They will talk to you about your blood results and ask how you have been feeling. If your blood results are okay, the pharmacy team will prepare your chemotherapy.

Your nurse usually gives you anti-sickness (anti-emetic) drugs before the chemotherapy. You may have the chemotherapy drugs through:

  • a cannula – a short, thin tube the nurse puts into a vein in your arm or hand
  • a central line – a fine tube that goes under the skin of your chest and into a vein close by
  • a PICC line – a fine tube that is put into a vein in your arm and goes up into a vein in your chest
  • an implantable port (portacath) – a disc that is put under the skin on your chest or arm and goes into a vein in your chest.

You will have each drug separately through a drip (infusion). You usually have the infusion through a pump. This gives you the treatment over a set time.

Ifosfamide can irritate the bladder lining and cause bleeding or discomfort when you pass urine (pee). To help prevent this, you will have a drug called mesna.

Mesna can be given as:

  • an infusion into a vein
  • a liquid to drink
  • tablets.

Mesna is not a chemotherapy drug.

Your course of chemotherapy

R-ICE is given as a course of several cycles of treatment over a few months. You may have a course of up to 6 cycles. Your doctor, nurse or pharmacist will talk to you about how the treatment will be given.

Each cycle of R-ICE is usually 21 days. You have treatment for the first 3 days of each cycle. R-ICE can be given in different ways. A common way is:

On day 1, your nurse will give you:

  • rituximab as an infusion
  • etoposide as an infusion - this takes 1 hour.

On day 2, your nurse will give you:

  • etoposide as an infusion - this takes 1 hour
  • carboplatin as an infusion - this takes 30 minutes to 1 hour
  • mesna as an infusion or injection into the vein - this takes 5 to 15 minutes
  • ifosfamide and mesna as infusions - this takes 24 hours.

You may also have some extra fluids with mesna in.

On day 3, your nurse will give you:

  • etoposide as an infusion - this takes 1 hour
  • mesna as an infusion - this takes 8 to 12 hours. This infusion starts when the 24-hour infusion of ifosfamide and mesna from day 2 has finished. You may have mesna as tablets instead of an infusion.

After this, you have a rest period with no chemotherapy for 18 days. Then you start the next cycle of your treatment.

About side effects

We explain the most common side effects of this treatment here. We also include some that are less common.

You may get some of the side effects we mention, but you are unlikely to get all of them. And you may have some side effects, including rarer ones, that we have not listed here. 

Always tell your doctor, nurse or pharmacist about any side effects you have. They can give you: 

  • drugs to help control some side effects
  • advice about managing side effects. 

It is important to take any drugs exactly as explained. This means they will be more likely to work for you. 

Serious and life-threatening side effects

Some cancer treatments can cause serious side effects. Sometimes, these may be life-threatening. Your doctor, nurse or pharmacist can explain the risk of these side effects to you.

Contact the hospital

Your doctor, nurse or pharmacist will give you 24-hour contact numbers for the hospital. If you feel unwell or need advice, you can call at any time of the day or night. Save these numbers in your phone or keep them somewhere safe.

Side effects while treatment is being given

Some people may have side effects while they are being given the chemotherapy or shortly after they have it:

Allergic reaction

Some people have an allergic reaction to rituximab or the chemotherapy drugs while they are having them.

With rituximab, it is the first infusion that is the most likely to cause a reaction. The first infusion is usually given more slowly than later rituximab treatments.

Before treatment, you will be given medicines to help prevent or reduce any reaction.

Signs of a reaction can include:

  • feeling hot or flushed
  • shivering
  • itching
  • a skin rash
  • feeling dizzy or sick
  • a headache
  • feeling breathless or wheezy
  • swelling of your face or mouth
  • pain in your back, tummy (abdomen) or chest.

Your nurse will check you for signs of a reaction during your drug infusions. If you feel unwell or have any of these signs, tell them straight away. If you do have a reaction, they can treat it quickly.

Sometimes a reaction happens a few hours after treatment. If you develop any signs or feel unwell after you get home, contact the hospital straight away.

Blood pressure

Some people's blood pressure falls while they are having rituximab. If you usually take medicine to lower your blood pressure, your doctor may ask you not to take it for 12 hours before having rituximab. Sometimes, rituximab can make your blood pressure go up. Your nurse will check your blood pressure regularly.

Tumour pain

During the rituximab infusion, you may have mild pain in the parts of the body where you have cancer. You may be given painkillers to help with this.

The drug leaks outside the vein

The drug may leak outside the vein. If this happens it can damage the tissue around the vein. This is called extravasation. Extravasation is not common but if it happens it is important that it is dealt with quickly. Tell your nurse straight away if you have any stinging, pain, redness or swelling around the vein. 

Pain along the vein

This treatment can cause pain:

  • at the place where the drip (infusion) is given 
  • along the vein. 

If you feel pain, tell your nurse straight away. They can check the site. They may give the drug more slowly or flush it through with more fluid to reduce pain.

Common side effects

Risk of infection

This treatment can reduce the number of white blood cells in your blood. These cells fight infection. If the number of white blood cells is low, you are more likely to get an infection. A low white blood cell count is sometimes called neutropenia.

Your doctor may give you antibiotics and other drugs to try to stop you getting an infection. These are called prophylactic medicines.

An infection can be very serious when the number of white blood cells is low. It is important to get any infection treated as soon as possible. Contact the hospital straight away on the 24-hour contact number you have been given if:

  • your temperature goes over 37.5°C (99.5°F)
  • you suddenly feel unwell, even with a normal temperature
  • you have symptoms of an infection
  • your temperature goes below 36°C (96.8°F).

Symptoms of an infection include:

  • feeling shivery and shaking
  • a sore throat
  • a cough
  • breathlessness
  • diarrhoea
  • needing to pass urine (pee) a lot, or discomfort when you pass urine.

It is important to follow any specific advice your cancer treatment team gives you.

The number of white blood cells will usually return to normal before your next treatment. You will have a blood test before having more treatment. If your white blood cell count is low, your doctor may delay your treatment for a short time, until your cell count increases.

From around day 6 of the cycle, you will be given a drug called G-CSF. This encourages the body to make more white blood cells. You usually have it once a day for a few days. It is given as a small injection under the skin. Your doctor can tell your more about this.

Bruising and bleeding

This treatment can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot.

If the number of platelets is low, you may bruise or bleed easily. You may have:

  • nosebleeds
  • bleeding gums
  • heavy periods
  • blood in your urine (pee) or stools (poo)
  • tiny red, brown or purple spots that may look like a rash – these spots can be harder to see if you have black or brown skin. 

If you have any unexplained bruising or bleeding, contact the hospital straight away on the 24-hour number. You may need a drip to give you extra platelets. This is called a platelet transfusion.

Anaemia (low number of red blood cells)

This treatment can reduce the number of red blood cells in your blood. Red blood cells carry oxygen around the body. If the number of red blood cells is low, this is called anaemia. You may feel:

  • very low in energy
  • breathless 
  • dizzy and light-headed. 

If you have these symptoms, contact the hospital straight away on the 24-hour number. You may need treatment for anaemia. If you are very anaemic, you may need a drip to give you extra red blood cells. This is called a blood transfusion.

Feeling sick

The nurses will give you anti-sickness drugs regularly to help prevent or control sickness during your treatment. If you feel sick or are sick (vomit), tell your nurse or doctor. They may change the anti-sickness drug to one that works better for you for the rest of the treatment cycles.

When you go home, your doctor will give you anti-sickness drugs to help prevent or control sickness. Take the drugs exactly as your nurse or pharmacist tells you. It is easier to prevent sickness than to treat it after it has started.

If you feel sick, take small sips of fluids often and eat small amounts regularly. It is important to drink enough fluids. If you continue to feel sick, or are sick (vomit) more than once in 24 hours, contact the hospital as soon as possible. They will give you advice. Your doctor or nurse may change the anti-sickness drug to one that works better for you.

Bladder irritation

Ifosfamide can irritate the lining of your bladder. It can cause bleeding or discomfort when you pass urine (pee). You will have urine tests before, during and after each cycle of treatment.

Drink at least 2 litres (3½ pints) of fluids during the 24 hours after chemotherapy. It is also important to empty your bladder regularly. Try to pee as soon as you feel the need to go.

To help prevent bladder irritation, the nurse will give you fluids through a drip (infusion) along with the chemotherapy. They will also give you a drug called mesna. You will be given this as an infusion, as a liquid to drink or as a tablet.

Contact the hospital straight away if you have any of the following when you pee:

  • discomfort
  • stinging
  • blood in your pee.

Hair loss

Your hair will get thinner. Or you may lose all the hair from your head. You may also lose your eyelashes and eyebrows, as well as other body hair. Hair loss usually starts after your first or second treatment.

If you want to cover up hair loss, there are different ways you can do this. Your nurse will give you information about coping with hair loss

Remember to protect your skin from the sun. Use suncream with a sun protection factor (SPF) of at least 30 on your scalp. Or cover up with a hat or scarf.

Hair loss is almost always temporary. Your hair will usually grow back after treatment ends.

Diarrhoea

This treatment may cause diarrhoea. Diarrhoea means passing more stools (poo) than is normal for you, or having watery or loose stools. You may also have stomach cramps. If you have a stoma, it may be more active than usual. 

If you are passing loose stools 3 or more times a day and this is not normal for you, contact the hospital as soon as possible on the 24-hour number. Follow the advice they give you about:

  • taking anti-diarrhoea medicines 
  • drinking enough fluids to keep you hydrated and to replace lost salts and minerals
  • any changes to your diet that might help. 

They might also ask you for a specimen of your stool to check for infection.

Sore mouth and throat

This treatment may cause a sore mouth and throat. You may also get mouth ulcers. This can make you more likely to get a mouth or throat infection. Use a soft toothbrush to clean your teeth or dentures in the morning, at night and after meals.

Contact the hospital straight away on the 24-hour number, if:

  • a sore mouth or throat affects how much you can drink or eat 
  • your mouth, tongue, throat or lips have any blisters, ulcers or white patches. 

They can give you advice, and mouthwash or medicines to help with the pain or to treat any infection. Follow their advice and make sure you:

  • drink plenty of fluids
  • avoid alcohol and tobacco
  • avoid food or drinks that irritate your mouth and throat.

Changes to your taste

Some foods may taste different or have no taste. Try different foods to find out what tastes best to you. You may also get a bitter or metallic taste in your mouth. Your doctor, nurse or pharmacist can give you advice. It might help to try:

  • sucking sugar-free sour or boiled sweets
  • eating cold foods
  • eating sharp-tasting fresh fruit.

Taste changes usually get better after treatment ends. We have more information about coping with changes to taste.

Skin changes

This treatment may affect your skin. It can cause a rash, which may be itchy. If your skin feels dry, try using an unperfumed moisturising cream every day. Your doctor, nurse or pharmacist can tell you how your skin may be affected and what will help.

During treatment, and for some months after, you will be more sensitive to the sun. Your skin may burn more easily. Cover up with clothing and a hat. If you are out in the sun, use a sun cream with a high sun protection factor (at least SPF 30) to protect your skin.

Your skin may get darker, but it will return to its normal colour after you finish treatment. If you have had radiotherapy, the area that was treated may become red or sore.

Always tell your doctor or nurse about any skin changes. They can give you advice and may prescribe creams or medicines to help. Any changes to your skin are usually temporary and improve when treatment finishes.

Rarely, a much more serious skin condition can develop. You may have a skin rash which then blisters, and your skin can peel. You may also feel unwell with flu-like symptoms such as a high temperature and joint pain. Contact the hospital straight away if this happens.

Feeling tired

Feeling tired is a common side effect of this treatment. It is often worse towards the end of treatment and for some weeks after it ends. Try to pace yourself and plan your day so you have time to rest. Gentle exercise, like short walks, can help you feel less tired. 

If you feel sleepy, do not drive or use machinery.

Loss of appetite

This treatment can affect your appetite. Don’t worry if you do not eat much for 1 or 2 days. But if your appetite does not come back after a few days, or if you are losing weight, tell your doctor, nurse or pharmacist. They can give you advice. They may give you food or drink supplements. Or they may suggest changes to your diet or eating habits to help.

Raised blood sugar levels

This treatment may raise your blood sugar levels and increase the risk of diabetes. 

You will have regular blood tests to check this. 

Signs of raised blood sugar include:

  • feeling thirsty
  • needing to pass urine (pee) more often than usual
  • feeling more tired than usual.

Contact the hospital on the 24-hour number if you have these symptoms during treatment or after it ends.

If you already have diabetes, your blood sugar levels may be higher than usual. You may need advice and support from your GP or diabetes team about managing this.

Constipation

This treatment can cause constipation. Constipation means that you are not able to pass stools (poo) as often as you normally do. It can become difficult or painful. Here are some tips that may help:

  • Drink at least 2 litres (3½ pints) of fluids each day.
  • Eat high-fibre foods, such as fruit, vegetables and wholemeal bread.
  • Do regular gentle exercise, like going for short walks.

If you have constipation, contact the hospital on the 24-hour number for advice. They can give you drugs called laxatives to help. 

If you have not been able to pass stools for over 2 days and are being sick, contact the 24-hour number straight away. 

Tummy pain

You may get pain in your tummy (abdomen), or have indigestion. Your doctor, nurse or pharmacist can give you advice or treatment to help. Contact the hospital straight away on the 24-hour number if your symptoms do not go away, or get worse.

Muscle or joint pain

You may get pain in your muscles or joints for a few days after treatment. If this happens, tell your doctor, nurse or pharmacist. They can give you painkillers and advice. They can also tell you if any of the painkillers you usually take are suitable. 

Tell them if the pain does not get better. Having warm baths and resting regularly may help. 

Less common side effects

Numb or tingling hands or feet (peripheral neuropathy)

This treatment may affect the nerves in your fingers and toes. This can cause numbness, tingling or pain in your hands or feet. This is called peripheral neuropathy. You might find it hard to do fiddly tasks such as fastening buttons or tying shoelaces.

If you have these symptoms, always tell your doctor, nurse or pharmacist. They sometimes need to change the drug or the dose of the drug. The symptoms usually improve slowly after treatment ends. But for some people they continue and are a long-term side effect of treatment.

Effects on the heart

This treatment can affect how the heart works. You may have tests to check how well your heart is working. These may be done before, during and after treatment.

If the treatment is causing heart problems, your doctor may change the type of treatment you are having.

Contact the hospital straight away on the 24-hour number if you have any of these symptoms during or after treatment:

  • breathlessness
  • dizziness
  • changes to your heartbeat
  • swollen feet and ankles.

Other conditions can cause these symptoms, but it is important to get them checked by a doctor. 

Always call 999 if you have:

  • chest pain, pressure, heaviness, tightness or squeezing across the chest
  • difficulty breathing.

Effects on the kidneys

This treatment can affect how the kidneys work. This is usually mild and goes back to normal after treatment ends. You will have blood tests to check how well your kidneys are working. Contact the hospital on the 24-hour number if you:

  • have blood in your urine (pee) 
  • are passing less urine or peeing less often than usual.

Drinking fluids helps protect your kidneys. The advice is usually to try to drink at least 2 litres (3½ pints) of fluid each day. But follow any advice from your doctor, nurse or pharmacist about how much is right for you.

Effects on the liver

This treatment may affect how your liver works. This is usually mild. You will have blood tests to check how well your liver is working.

Mood and sleep changes

You may have some mood changes during this treatment. You may feel low, depressed or anxious. You may have trouble sleeping. Tell your doctor or nurse if you notice any changes.

Effects on the brain

Ifosfamide can affect the brain. Contact the hospital straight away if you notice any changes such as:

  • unsteadiness
  • feeling drowsy or confused
  • problems with moving or speaking

It is important not to drive or operate machinery if you have these side effects. If you are at risk of these effects, your doctors may give you a drug called methylene blue to help prevent them.

Rarely, this treatment can cause a condition called posterior reversible encephalopathy syndrome (PRES). This is sometimes called reversible posterior leukoencephalopathy syndrome (RPLS). This condition can cause:

  • a headache that does not get better
  • drowsiness or confusion
  • changes in eyesight
  • fits (seizures).

If you have any of these symptoms, you should either:

  • call the 24-hour emergency number the hospital has given you
  • go to the hospital straight away.

You should not drive yourself to hospital.

You can make a full recovery from PRES. But it needs to be diagnosed and treated quickly.

Tumour lysis syndrome (TLS)

Some people are at risk of developing a condition called tumour lysis syndrome (TLS) during this treatment. When treatment makes large numbers of cancer cells die and break down quickly, they release lots of waste products into the blood. This can affect how well the kidneys work. It may also cause problems with the heart rhythm.

TLS can be prevented. You will have regular blood tests to check for TLS. If you are at risk of TLS, you may have:

  • extra fluids through a drip
  • medicines such as rasburicase through a drip, or allopurinol as tablets.

Drinking at least 2 litres (3½ pints) of fluid a day will also help.

Hearing changes

This treatment may cause ear pain or hearing changes, including hearing loss. You may have ringing in the ears. This is called tinnitus. You may also become unable to hear some high-pitched sounds. Hearing changes usually get better after this treatment ends. But some can be permanent. Tell your doctor if you notice any changes in your hearing.

Eye problems

This treatment may make your eyes feel sore, red and itchy (conjunctivitis). Your doctor will prescribe eye drops to help. It is important to use these as instructed.

Always tell your doctor or nurse if you have pain or notice any change in your vision.

Effects on the lungs

This treatment can cause changes to the lungs. Tell your doctor, nurse or pharmacist if you develop: 

  • a cough that does not go away
  • wheezing
  • breathlessness.

You should also tell them if any existing breathing problems get worse. You may have tests to check your lungs.

Hepatitis B reactivation

If you have had hepatitis B (a liver infection) in the past, rituximab can make it active again. Your doctor or nurse will talk to you about this and test you for hepatitis B.

If your test shows that you have had it in the past you may be given treatment to prevent it becoming active again.

If you have active hepatitis B, you will not have treatment with rituximab.

Second cancer

This treatment can increase the risk of developing a second cancer years later. But this is rare.

You can talk to your doctor or nurse about this. They can explain how the benefits of your treatment will outweigh the risk.

Other important information

Blood clot risk

Cancer and some cancer treatments can increase the risk of a blood clot. Contact the hospital straight away on the 24-hour number if you have any of these symptoms during or after treatment:

  • throbbing pain or swelling in a leg or arm
  • reddening of the skin in the area – if you have black or brown skin, this can be harder to notice, but the skin might become darker
  • suddenly feeling breathless or coughing.

Always call 999 if you have:

  • chest pain
  • difficulty breathing.

A blood clot is serious, but it can be treated with drugs called anticoagulants. These thin the blood. Your doctor, nurse or pharmacist can give you more information about preventing and treating blood clots.

Alcohol

Some preparations of this treatment contain alcohol. If having alcohol is a problem for you, tell your doctor, nurse or pharmacist. Your blood alcohol level may be above the legal limit after you have the treatment. Do not drive or operate machinery for a few hours after having this treatment, even if you feel okay.

Other medicines

Some medicines can affect how this treatment works or be harmful while you are having it. Always tell your cancer doctor, nurse or pharmacist about any drugs you are taking or planning to take, such as: 

Vaccinations

Doctors usually recommend that people with cancer have vaccinations for flu and for coronavirus (covid). These help reduce your risk of serious illness from these infections. Most people can have these vaccines, including people with weak immune systems.

If your immune system is weak, you should not have live vaccinations. Live vaccines can make you unwell because they contain a very weak version of the illness they will protect you against. Live vaccines include Zostavax®, which is a shingles vaccine, and the yellow fever vaccine.

It is important to ask your doctor, nurse or pharmacist for advice about having vaccinations. They can explain what vaccines are right for you and when it is best to have them.

Contraception

Your doctor, nurse or pharmacist will advise you not to get pregnant or make someone pregnant while having this treatment and for some time afterwards. The drugs may harm a developing baby. It is important to use contraception to prevent pregnancy. Follow their advice about:

  • what types of contraception to use 
  • how long after treatment you should continue to use contraception. 

Breastfeeding

You are advised not to breastfeed while having this treatment, or for some time after treatment ends. This is because the drugs could be passed to the baby through breast milk. 

Your doctor, nurse or pharmacist can give you more information.

Fertility

Some cancer drugs can affect whether you can get pregnant or make someone pregnant. If you are worried about this, it is important to talk with your doctor before you start treatment.

Changes to periods

If you have a period, these may become irregular or stop while you are having this treatment. This may be temporary, but it can sometimes be permanent. Your menopause may start sooner than it would have done. Your doctor or nurse can give you more information.

Sex

It is possible that small amounts of chemotherapy may be passed on through vaginal fluids or semen. If you have sex in the first few days after treatment, your cancer team will usually advise using condoms or a dental dam to protect your partner.

Medical and dental treatment

If you need medical treatment for any reason other than cancer, always tell the healthcare professional that you are having cancer treatment. Give them the contact details for your cancer doctor or cancer team so they can ask for advice.

If you have appointments with a dentist, always tell them you are having cancer treatment. Talk to your cancer team before you have any dental treatment.

About our information

  • Reviewers

    This information has been written, revised and edited by Macmillan Cancer Support’s Cancer Information Development team. It has been reviewed by expert health professionals and people living with cancer.

    Our cancer information has been awarded the PIF TICK. Created by the Patient Information Forum, this quality mark shows we meet PIF’s 10 criteria for trustworthy health information.

The language we use

We want everyone affected by cancer to feel our information is written for them.

We want our information to be as clear as possible. To do this, we try to:

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  • use illustrations to explain text
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We use gender-inclusive language and talk to our readers as ‘you’ so that everyone feels included. Where clinically necessary we use the terms ‘men’ and ‘women’ or ‘male’ and ‘female’. For example, we do so when talking about parts of the body or mentioning statistics or research about who is affected.

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Date reviewed

Reviewed: 01 October 2023
|
Next review: 01 October 2025
Trusted Information Creator - Patient Information Forum
Trusted Information Creator - Patient Information Forum

Our cancer information meets the PIF TICK quality mark.

This means it is easy to use, up-to-date and based on the latest evidence. Learn more about how we produce our information.