ESHAP and R-ESHAP chemotherapy
This information is about two similar chemotherapy treatments for lymphoma, called ESHAP and R-ESHAP. Your hospital doctor or nurse will explain which one you will be having.
The drugs that are used
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ESHAP is named after the drugs used in the treatment, which are:
R-ESHAP also includes the monoclonal antibody drug rituximab (Mabthera®).
Rituximab belongs to a group of 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 to 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 and on some of the abnormal B-cells found in 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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ESHAP or R-ESHAP treatment is usually given to you during a short stay in hospital. Before you start treatment you will need to have a blood test either on the same day or a few days beforehand. 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. All of this may take a couple of hours.
ESHAP 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 the arm (PICC line). All of the chemotherapy drugs are given as a drip (infusion). Your doctor or nurse will explain more about this.
You'll be given some anti-sickness (anti-emetic) medicines. These are usually given by injection through the central line or PICC line, which is connected to a drip (infusion). Some anti-sickness medicines are given as tablets.
If you're being treated with R-ESHAP, the rituximab (a colourless fluid in a drip bag) is given as an infusion into your central or PICC line. The first dose of rituximab is given slowly over a few hours, as some people can have an allergic reaction to it. You'll be given medication to help reduce the chances of an allergic reaction.
If you have an allergic reaction, the drip can be stopped and started again more slowly when the symptoms have reduced. You should be able to have later doses of rituximab more quickly.
While having ESHAP or R-ESHAP chemotherapy you will also be given infusions of fluid to help keep your kidneys working normally. This is sometimes known as hydration. You may be given a drug called mannitol, which is given as an infusion with the cisplatin. Mannitol increases the amount of urine that your kidneys produce.
How often treatment is given
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Your doctor may use the word 'regimen' (eg the ESHAP regimen) when talking about your chemotherapy. This means the whole plan or schedule of the particular treatment you're having. The treatment is planned over a period of five days.
If you're having rituximab as part of R-ESHAP, you'll have this first. The other drugs are usually given as follows:
Cytarabine (a colourless fluid) is given as an infusion, usually over two hours. Cytarabine is either given on day one or day five; you will only have one dose.
Etoposide (a colourless fluid) is given as an infusion over about one hour. Etoposide is given once a day on days 1–4.
Cisplatin (a colourless fluid) is given as an infusion over about 23 hours. Cisplatin is given once a day on days 1–4.
Methylprednisolone (a colourless fluid) is given as an infusion over 15–30 minutes. Methylprednisolone is given once a day on days 1–5.
Because lots of drug and fluid infusions are given in ESHAP treatment, it may sound difficult to fit them all into one day. However, it's possible to run two infusions at one time using a central or PICC line. Your doctor or chemotherapy nurse will tell you more about this.
When all of the chemotherapy has finished, you can go home. Before going home you'll be given some steroid eye drops to take for the next 5–7 days, which can help prevent sore eyes. You'll also be given a supply of anti-sickness (anti-emetic) tablets to take with you. It's important to take these as directed, even if you aren't feeling sick. This is because some anti-sickness drugs are much better at preventing sickness than at stopping it once it starts.
You'll then have a rest period with no treatment for either 16 or 23 days (your doctor will explain which). This completes what is called a cycle of your chemotherapy treatment. Each cycle takes 21 or 28 days (three or four weeks).
You'll start the next cycle of your treatment after the rest period.
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 ESHAP or R‑ESHAP chemotherapy.
We have outlined the most common side effects but haven't included those that are rare and unlikely to affect you. If you notice any effects that aren't listed here, discuss them with your doctor, chemotherapy nurse or pharmacist.
Risk of infection
ESHAP and R-ESHAP 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'll be more prone to infections. A low white blood cell count is called neutropenia.
Neutropenia 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).
You may also be given antibiotics (known as prophylactic antibiotics) to help prevent infections.
Bruising or bleeding
ESHAP and R-ESHAP can reduce the production of platelets, which help 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.
ESHAP and R-ESHAP 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 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.
Your kidneys may be affected
Cisplatin can affect your kidneys. This doesn't usually cause any symptoms and the effect is generally mild. Rarely, it may cause permanent damage to the kidneys unless the treatment is stopped.
Before each treatment, your kidneys will be checked by a blood test. You’ll be given fluid through a drip (infusion) before and after the treatment to keep your kidneys working normally. You may be asked to measure and record what you drink and the amount of urine you pass. It’s important to tell your nurse or doctor if you pass less urine than usual.
If necessary, you may be given medicine to help you to 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.
Some people have an allergic reaction to rituximab while it’s being given. Signs of this include flu-like symptoms (headache, fever high temperature or chills), feeling sick, skin rashes and itching, breathlessness, or pain in your back, tummy or chest.
It‘s most common with the first infusion, so the first dose is given slowly over a number of hours. You’ll also be given medicines before the treatment to help prevent or reduce any reaction. You’ll be monitored closely during your infusion but it's important to tell your nurse or doctor if you feel unwell or have any of the above symptoms. If you do have a reaction, it can be treated quickly.
You may develop flu-like symptoms a few hours after the treatment has been given. These include headaches, aching joints or muscles, a temperature, lack of energy (lethargy) and chills. If this happens, it's important to drink plenty of fluids and get some rest.
If these symptoms continue for more than a day, contact your doctor.
Low blood pressure
This may happen during the infusion of rituximab, so your blood pressure will be regularly checked.
If you usually take drugs to lower your blood pressure your doctor may advise you to take these at least 12 hours before you have rituximab. It’s important not to do this without discussing it with your doctor first.
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. Your nurse will show you how to use these. Let your doctor know if you develop any problems, as you may need painkillers or antibiotics if your mouth becomes sore and infected.
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 taking some gentle exercise, such as short walks, which will help. If tiredness is making you feel sleepy, don’t drive or operate machinery.
This treatment may cause an inflammation of the lining of the eyelids (conjunctiva) that makes your eyes feel sore, red and itchy. You'll be given steroid eye drops to prevent this side effect from occurring. It’s important to follow the instructions you are given.
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.
Irritation of stomach lining
Methylprednisolone can irritate the lining of the stomach and may cause a stomach ulcer or make one worse. To help reduce this effect, methylprednisolone is usually given as an intravenous injection rather than by mouth. Tell your doctor if you have any indigestion, or pain or discomfort in the tummy (abdomen). Your doctor may prescribe drugs to reduce irritation of the stomach.
Raised blood sugar
This may happen if you’re having high-dose or ongoing treatment with methylprednisolone (a steroid). During your treatment with steroids your blood sugar levels will be checked with regular blood tests. Your urine may also be tested regularly for sugar.
Tell your doctors if you get very thirsty or if you’re passing more urine than usual. This can be a sign that your blood sugar level is rising.
People with diabetes should be more careful than usual when checking their blood sugar levels. You should tell your doctor if you have any problem controlling your diabetes.
Less common side effects
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This can usually be controlled easily with medicine, but tell your doctor if it is severe or if it continues. It's important to drink plenty of fluids if you do have diarrhoea. If you have any change in bowel habit, tell your doctor.
Changes in hearing
Cisplatin may cause ringing in the ears (tinnitus) and you may lose the ability to hear some high-pitched sounds. Hearing loss can be more severe with higher doses and longer courses of treatment. Very occasionally, your sense of balance may be affected. Any hearing loss, and balance changes if they occur, may be permanent. However tinnitus usually improves when treatment ends. Tell your doctor if you notice any loss of hearing or tinnitus.
Numbness or tingling in hands or feet
This is due to the effect of cisplatin on nerves and is known as peripheral neuropathy. Tell your doctor if you notice these symptoms or have difficulty carrying out fiddly tasks.
It's important to report your symptoms to your doctor as they may be controlled by slightly lowering the dose of the drug.
This side effect usually improves slowly a few months after the treatment has finished. Sometimes symptoms can persist; talk to your doctor if this happens.
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.
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.
Behavioural changes and mood swings
Occasionally, steroids can cause mood swings, difficulty sleeping and perhaps anxiety or irritability. Let your doctor know if there are any changes in your behaviour that are worrying you. Difficulty with sleeping may be helped by having the steroids in the early part of the day; discuss this with your doctor to see if this is possible.
Etoposide can cause a rash, which may be itchy. Your doctor can prescribe medicine to help with this. Your skin may darken due to excess production of pigment. It usually returns to normal a few months after the treatment has finished.
Cytarabine can cause soreness and redness of the palms of the hands and soles of the feet. This is temporary and usually improves once treatment finishes. Let your doctor know if this happens.
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 your risk of developing a blood clot (thrombosis), and having 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 is important to tell your doctor straight away if you have any of these symptoms. Most clots can be treated with drugs that thin the blood. Your doctor or nurse can give you more information.
Some medicines, including those you can buy in a shop or chemist, may 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 taking this treatment as it may harm the developing baby. It is important to use effective contraception while taking this drug, and for some time 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.
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 upon our ESHAP and R‑ESHAP 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.