ICE and R-ICE chemotherapy for lymphoma
This information is about two similar chemotherapy treatments for lymphoma called ICE and R-ICE. It can also be given to treat other types of cancer.
The drugs that are used
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ICE is named after the initials of the chemotherapy drugs used, which are:
R-ICE also includes the monoclonal antibody drug rituximab (Mabthera®).
Rituximab belongs to a group of cancer drugs known as monoclonal antibodies.
It's used to treat several different kinds of B-cell non-Hodgkin lymphoma.
Monoclonal antibodies recognise and lock on to specific proteins on the surface of cancer cells. This helps the body's immune system recognise the cancer cells and destroy them. Monoclonal antibodies are sometimes called targeted therapies because they target cancer cells.
Rituximab locks on to a protein called CD20, which is found on the surface of white blood cells called B-lymphocytes or B-cells. This triggers the body’s immune system to attack the cells and destroy them.
As well as being found on the surface of normal B-cells, CD20 is also present on most of the abnormal B-cells that occur in many types of non-Hodgkin lymphoma. It also occurs on some of the abnormal B-cells found in chronic lymphocytic leukaemia (CLL).
Rituximab destroys both abnormal (malignant) and normal B-cells. However, the body can replace normal B-cells that are damaged so their numbers recover once treatment is over.
How treatment is given
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ICE and R-ICE treatment can usually be given during a short stay in hospital. Before you start your treatment, you will need to have a blood test – either on the same day or a few days before. You will also be seen by a doctor, specialist nurse or pharmacist. If the results of your blood test are normal, the pharmacy will prepare your chemotherapy drugs. This may take a couple of hours.
ICE and R-ICE chemotherapy is usually given through a thin, plastic tube that is inserted under the skin and into a vein near the collarbone (central line), or passed through a vein in the crook of your arm (PICC line). Your doctor or nurse will explain more about this to you.
If you do not have a line, the nurse will put a thin, flexible tube (cannula) into a vein in your hand or arm. You may find this uncomfortable or a little painful, but it shouldn't take long.
Before the chemotherapy you'll be given some anti-sickness (anti-emetic) drugs. These are usually given by injection through the central line, PICC line or cannula, which is connected to a drip (infusion).
Some anti-sickness medicines are given as tablets. The chemotherapy drugs are then given separately as infusions. They are all colourless fluids.
If you are being treated with R-ICE, the rituximab (a clear fluid in a drip bag) is given as an infusion into your cannula or line. The first dose of rituximab is given slowly over a few hours, as some people can have an allergic reaction to it.
If you have a reaction, the drip can be stopped and started again more slowly when symptoms have calmed down. You should be able to have your second and subsequent doses of rituximab more quickly.
Ifosfamide can irritate the bladder lining and cause bleeding. To help prevent this, a drug called mesna (Uromitexan®) is given. The mesna can be mixed with the ifosfamide, or given shortly after the ifosfamide as a separate infusion. Sometimes, mesna may be given as tablets that you can take at home. It's very important that you take the tablets exactly as they are prescribed.
Once treatment has finished you can go home. If you have a cannula it will be removed before you go. If you have a central or PICC line it will usually stay in place, ready for the next cycle of your chemotherapy. You will be shown how to look after the line.
You will be given a supply of anti-sickness drugs to take home with you. It's important to take these as directed, even if you aren't feeling sick, as some anti-sickness drugs are much better at preventing sickness than at stopping it once it starts.
How often treatment is given
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Your doctor may use the word 'regimen’ (eg the ICE regimen) when talking about your chemotherapy. This means the whole plan or schedule of your particular chemotherapy treatment.
ICE and R-ICE chemotherapy can be given in slightly different ways. The following are descriptions of three commonly used schedules. You can ask your doctor or nurse to tell you whether you'll be having one of these regimens. If not, they can explain your regimen to you.
R-ICE chemotherapy is given in cycles that are repeated, usually three times, to make up a course of treatment.
Two days before you start your first cycle, you'll be given an infusion of rituximab. On the first day of the cycle, you'll be given another infusion of rituximab. Two days later (day three) you'll be given a short infusion of etoposide. On the next day (day four), the etoposide will be repeated. You'll also be given an infusion of carboplatin and start a 24-hour infusion of ifosfamide and mesna that have been mixed together. On the fifth day of the cycle, you'll finish the ifosfamide and mesna infusion and be given etoposide for a third time. After this, you can go home.
Two days later (day seven of the cycle) you'll start daily injections of a drug called G-CSF (granulocyte-colony stimulating factor). This is a type of protein that stimulates the bone marrow to produce more white blood cells. The injections are given under the skin (subcutaneously). The G-CSF injections are given for eight days (days 7–14). This completes one cycle of your treatment. Each cycle lasts for 14 days.
On the next day you'll start your next cycle of treatment, starting again from day one. The same drugs will be given to you again, except for the initial infusion of rituximab which is only given before the first cycle. Usually three cycles of treatment are given.
On the first day of ICE chemotherapy, you will be given all three chemotherapy drugs (ifosfamide, carboplatin and etoposide). The infusions of carboplatin and etoposide are both given over about an hour, and the ifosfamide lasts for about six hours.
On the next day (day two), you'll be given three more infusions of ifosfamide, each lasting six hours, and an infusion of etoposide, which will last for an hour. You will also be given a six-hour infusion of mesna. After this you will have a rest period, with no chemotherapy for the next 19 days. This completes a cycle of your treatment. Each cycle lasts for 21 days (three weeks).
Following the rest period, and three weeks after you started, you'll be given the same drugs again, beginning your next cycle of your treatment. Usually three cycles of treatment are given over 2–3 months.
This makes up a course of treatment.
If you are following this schedule and also being given rituximab (R-ICE), you will be given an infusion of rituximab on the first day of each cycle.
On the first day of ICE chemotherapy, you'll be given an infusion of etoposidefor an hour. On the next day (day two) the etoposide will be repeated. You will also be given a 60-minute infusion of carboplatin and start a 24-hour infusion of ifosfamide and mesna.
On the following day (day three) you'll be given a third infusion of etoposide, again over about an hour. You will finish your 24-hour infusion of ifosfamide and mesna, and be given a 12-hour infusion of mesna on its own. After this, you'll have a rest period with no chemotherapy for 17 days. This completes a cycle of your treatment. Each cycle lasts for 21 days (three weeks).
After the rest period (three weeks after you started) the same drugs will be given to you again, beginning the next cycle of your treatment. Usually 2–4 cycles of treatment are given over 2–4 months. This makes up a course of treatment.
If you are following this schedule but also being given rituximab (R-ICE), you will be given an infusion of rituximab on the first day of each cycle.
Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described here won't affect everyone who is having ICE or R-ICE chemotherapy.
We have outlined the most common side effects and some of the less common ones, so that you can be aware of them if they occur. However, we haven't included those that are rare and unlikely to affect you. If you notice any effects that aren't listed here, please discuss them with your doctor, chemotherapy nurse or pharmacist.
Feeling sick (nausea) and being sick (vomiting)
Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce, nausea or vomiting. If the sickness isn't controlled, or if it continues, tell your doctor; they can prescribe other anti-sickness drugs that may be more effective.
Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.
Risk of infection
ICE and R-ICE can reduce the number of white blood cells, which help to fight infection. White blood cells are produced by the bone marrow. If the number of your white blood cells is low you will be more prone to infections. A low white blood cell count is called neutropenia.
This begins seven days after treatment and your resistance to infection is usually at its lowest 10–14 days after chemotherapy. The number of your white blood cells will then increase steadily and usually return to normal before your next cycle of chemotherapy is due.
Contact your doctor or the hospital straight away if:
your temperature goes above 38°C (100.4°F)
you suddenly feel unwell, even with a normal temperature.
You'll have a blood test before having more chemotherapy to check the number of white blood cells. Occasionally, your treatment may need to be delayed if your number of blood cells (blood count) is still low.
You may be given injections of G-CSF to help prevent the number of white blood cells getting too low. G-CSF is a type of protein that can stimulate the bone marrow to produce white blood cells. G-CSF is given as an injection under the skin (subcutaneously).
Bruising or bleeding
ICE and R-ICE can reduce the production of platelets, which help the blood to clot. Tell your doctor if you have any unexplained bruising or bleeding, such as nosebleeds, bleeding gums, blood spots or rashes on the skin. You can have a platelet transfusion if your platelet count is low.
ICE and R-ICE can reduce the number of red blood cells, which carry oxygen around the body. A low red blood cell count is called anaemia. This may make you feel tired and breathless. Tell your doctor or nurse if you have these symptoms. You may need to have a blood transfusion if the number of red blood cells becomes too low.
Feeling tired is a common side effect of chemotherapy especially towards the end of treatment and for some weeks after it’s over. It’s important to try to pace yourself and get as much rest as you need. Try to balance this with some gentle exercise, such as short walks, which will help. If tiredness is making you feel sleepy, don’t drive or operate machinery.
This usually starts 3–4 weeks after starting treatment, although it may occur earlier. Hair usually falls out completely. You may also have thinning and loss of eyelashes, eyebrows and other body hair. This is temporary and your hair will start to grow again once the treatment has finished. Your hair may grow back straighter, curlier, finer, or a slightly different colour than it was before. Your nurse can give you advice about coping with hair loss.
Ifosfamide may irritate the bladder. It’s important to drink as much fluid as you can (at least two litres a day) during the treatment. You’ll usually be given fluids through a drip (infusion), along with a drug called mesna (Uromitexan®) to help prevent bladder irritation. Your urine will be measured and tested for blood. If there’s any blood in your urine you’ll be given more mesna.
Loss of appetite
Some people lose their appetite while they’re having chemotherapy. This can be mild and may only last a few days. If it doesn’t improve you can ask to see a dietitian or specialist nurse at your hospital. They can give you advice on improving your appetite and keeping to a healthy weight.
Less common side effects
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Treatment with ICE or R-ICE may cause changes in the way your liver works, although it will return to normal when the treatment finishes. You're very unlikely to notice any problems but your doctor will take regular blood samples to check your liver is working properly.
A skin rash can sometimes occur while you're having treatment with ifosfamide. It’s important to let your doctor know if this happens. Your doctor can prescribe medicine to help with this.
Rarely, your skin may darken. If it does, it usually goes back to normal a few months after the treatment has finished. During treatment and for several months afterwards, you will be more sensitive to the sun and your skin may burn more easily than normal. You can still go out in the sun, but should wear a suncream with a high sun protection factor (SPF) and cover up with clothing and a hat.
Treatment with ICE or R-ICE can cause diarrhoea. This can usually be easily controlled with medicine but tell your doctor if it is severe or continues. It's important to drink plenty of fluids if you have diarrhoea.
Your kidneys may be affected
This doesn't usually cause any symptoms and the effect is generally mild. If the effect is severe, however, the kidneys can be permanently damaged unless the treatment is stopped. For this reason, your kidneys will be checked by a blood test before each treatment.
If necessary, you may be given medicine to help you pass urine. You may be asked to drink extra fluid before and after treatment. It’s important to do this, so let your doctor know if this is a problem, for example, if you are feeling sick.
Your mouth may become sore or dry, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Some people may find sucking on ice soothing. Tell your nurse or doctor if you have any of these problems, as they can prescribe mouthwashes and medicine to prevent or clear mouth infections.
You may notice that food tastes different. Normal taste usually comes back after treatment finishes. A dietitian or specialist nurse at your hospital can give you advice about ways of coping with this side effect.
Extreme drowsiness, loss of balance, hallucination and confusion
These are very rare side effects of ifosfamide and only occur with high-dose treatment. If you notice any of these effects it is important to tell your doctor straight away.
Pain along the vein
Etoposide can cause pain along the vein which is used to give you your chemotherapy. If you feel any pain, tell your doctor or nurse straight away so that they can check the infusion site. They may slow the infusion down to reduce pain.
It’s important to let your doctor know straight away if you feel unwell or have any severe side effects, even if they’re not mentioned above.
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Risk of developing a blood clot
Cancer can increase the risk of developing a blood clot (thrombosis), and chemotherapy may increase this risk further.
A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it’s important to tell your doctor straight away if you notice any of these symptoms. Most clots can be treated with drugs that thin the blood. The doctor or nurse can give you more information.
Some medicines, including those that you can buy in a shop or chemist, can be harmful to take when you are having chemotherapy. Tell your doctor about any medicines you are taking, including over-the-counter drugs, complementary therapies and herbal drugs.
Your ability to become pregnant or father a child may be affected by having this treatment. It's important to discuss fertility with your doctor before starting treatment.
It's not advisable to become pregnant or father a child while having ICE or R-ICE, as it may harm the developing baby. It’s important to use effective contraception while taking this drug, and for at least a few months afterwards. You can discuss this with your doctor.
It’s not known whether chemotherapy drugs can be present in semen or vaginal fluids. To protect your partner it’s safest to either avoid sex or use a barrier form of contraception for about 48 hours after chemotherapy.
There is a risk that chemotherapy drugs may be present in breast milk so women are advised not to breastfeed during chemotherapy and for a few months afterwards.
Loss of periods in women
Due to the effect of chemotherapy on the ovaries, women may find that their periods become irregular and they may eventually stop.
In some women this may be temporary, but for others it will be permanent. This will result in menopausal symptoms such as hot flushes, sweats and vaginal dryness.
Very rarely, etoposide may cause a second cancer, usually a type of acute leukaemia, to develop years later. Your nurse or doctor can discuss this with you.
If you’re admitted to hospital for a reason not related to the cancer, it’s important to tell the doctors and nurses looking after you that you are having chemotherapy treatment. You should tell them the name of your cancer specialist so that they can ask for advice.
It’s a good idea to know who you should contact if you have any problems or troublesome side effects when you’re at home. Your chemotherapy nurse or doctor will give you details of who to contact for advice. This should include ‘out-of hours’ contact details if you need to call someone at evenings, overnight or at the weekend.
This section is based on our ICE and R-ICE chemotherapy fact sheet, which has been compiled using information from a number of reliable sources, including:
Sweetman, et al. Martindale: The Complete Drug Reference. 37th edition. 2011. Pharmaceutical Press.
British National Formulary. 62nd edition. 2011. British Medical Association and Royal Pharmaceutical Society of Great Britain.
electronic Medicines Compendium (eMC). (accessed October 2011).
Perry MC. The Chemotherapy Source Book. 4th edition. 2007. Lippincott Williams and Wilkins.