This information is about two similar chemotherapy treatments for lymphoma, called ESHAP and R‑ESHAP. Your doctor or nurse will explain to you which one you will be having. If you have any questions you can ask your doctor or nurse at the hospital where you are having your treatment, or speak to one of our cancer information nurse specialists.

ESHAP is named after the chemotherapy drugs used in the treatment, which are:

• etoposide
• methylprednisolone, which is a steroid
• cytarabine, which is sometimes known as Ara C
• cisplatin, which contains platinum.

R-ESHAP also includes the drug rituximab (Mabthera®).

Rituximab

Rituximab is a monoclonal antibody. Monoclonal antibodies are used to try to destroy some types of cancer cells while causing little harm to normal cells. They are designed to recognise certain proteins that are found on the surface of some cancer cells. The monoclonal antibody recognises the protein and locks into it (like a key in a lock). This may then trigger the body’s immune system to attack the cancer cells and can sometimes cause the cells to destroy themselves.

Rituximab is used to treat several different types of B-cell non-Hodgkin's lymphoma. It locks onto a protein called CD20, which is found on the surface of one of the main types of normal white blood cells (B-cell lymphocytes). It is also present on the surface of most of the abnormal B-cell lymphocytes that occur in some types of non-Hodgkin's lymphoma. Rituximab acts by attacking both abnormal (malignant) and normal B-cell lymphocytes. However, the body can quite quickly replace any normal white blood cells that are damaged.

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 which is inserted under the skin and into a vein near the collarbone (central line), or passed through a vein in the arm (PICC line). Your doctor or nurse will explain more about this.

You will 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.

The chemotherapy and steroid drugs are then given separately:

• Etoposide (a colourless fluid) is given as an infusion, over about an hour.
• Methylprednisolone is given as an infusion, over 15–30 minutes.
• Cytarabine (a colourless fluid) is given as an infusion, over two hours.
• Cisplatin (a colourless fluid) is given as an infusion that lasts for 96 hours (four days).

If you are 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 (see Possible side effects). You will be given medication (chlorpheniramine and paracetamol) 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.

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 that you are receiving.

On the first day of your treatment you will be given infusions of etoposide and methylprednisolone, as described. You will also start the 96-hour infusion of cisplatin. If you are having R-ESHAP, you will be given an infusion of rituximab on the first day of your treatment, before the etoposide, methylprednisolone and cisplatin.

On the second day of your treatment the cisplatin infusion will continue. The etoposide and methylprednisolone infusions will be repeated. Days three and four are the same as day two.

On day five of your treatment you will finish your 96-hour cisplatin infusion and be given a further infusion of methylprednisolone. You will also be given an infusion of cytarabine.

When all of the chemotherapy has finished you can go home. Before going home you will be given some steroid eye drops to take for the next 5–7 days that can help to prevent sore eyes. You will be given a supply of anti-sickness (anti-emetic) tablets to take with you. It is important to take these as directed even if you are not feeling sick. This is because some anti-sickness drugs are much better at preventing sickness than at stopping it once it starts. Before going home you will be given some steroid eye drops to take for the next 5–7 days.

You will 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.

You will 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 in this information will not affect everyone who is having ESHAP or R‑ESHAP chemotherapy.

We have outlined the most common side effects, so that you can be aware of them if they occur. However, we have not included those that are rare and therefore unlikely to affect you. If you notice any effects that you think may be due to the drug, but which are not listed in this information, please let your nurse or doctor know.

Feeling sick (nausea) and being sick (vomiting) Your doctor can prescribe very effective anti-sickness (anti-emetic) medicines to prevent or reduce nausea and vomiting. If the sickness is not controlled, or if it continues, tell your doctor. They can prescribe other anti-sickness medicines which may be more effective. Some anti-sickness medicines can cause constipation. Let your doctor or nurse know if this is a problem.

Lowered resistance to infection ESHAP chemotherapy reduces the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given, with your resistance to infection usually reaching its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily and will usually have returned to normal levels before your next cycle of chemotherapy is due. You may be given antibiotics to take as a preventative measure (known as prophylactic antibiotics).

Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.4ºF)
• you suddenly feel unwell (even with a normal temperature).

You will have a blood test before having more chemotherapy to make sure that your number of white blood cells has returned to normal. Occasionally, it may be necessary to delay treatment if your number of blood cells (blood count) is still low.

You may be given injections of a drug called G-CSF (granulocyte-colony stimulating factor), which is a protein that can help to boost the number of white blood cells that your bone marrow produces. It is given as an injection under the skin (subcutaneously).

Bruising or bleeding ESHAP can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, and bleeding gums.

Anaemia (low number of red blood cells) While having this treatment you may become anaemic. This may make you feel tired and breathless. Let your doctor or nurse know if these effects are a problem.

Your kidney function may be affected Usually this does not cause any symptoms and any effect on your kidneys is generally mild. Rarely, it may cause permanent damage to the kidneys unless the treatment is stopped. Before each treatment you will have a blood test to check how well your kidneys are working. You will be asked to drink more than normal on the day after treatment. It is important to tell your doctor or chemotherapy nurse if you are not able to drink enough. Tell your doctor or nurse if you are passing less urine than normal.

Allergic reaction It is possible to have a slight allergic reaction to rituximab. Signs of this include skin rashes and itching, a feeling of swelling of the tongue or throat, irritation of the nasal passages, wheezing, a cough and breathlessness. You will be monitored closely during your treatment, but tell your doctor or nurse if you have any of these effects. Certain drugs (chlorpheniramine and paracetamol) can be given to reduce the chance of developing an allergic reaction. The rituximab infusion can also be slowed-down or stopped until the reaction is over.

Flu-like symptoms Some people find that rituximab can cause headaches, aching joints and muscles, a temperature, lethargy (feeling of having no energy) and chills. These side effects can occur while the drug is being given, but do not usually last long.

Low blood pressure This may happen during the infusion of rituximab, so your blood pressure will usually be regularly checked. People who normally take drugs to lower their blood pressure may be advised by their doctor to take these at least 12 hours before rituximab is given. It is important not to alter your blood pressure medication without first discussing it with your doctor.

Sore mouth and ulcers Your mouth may become sore, 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. You will be given mouthwashes to help keep your mouth clean and prevent infection. 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.

Tiredness Many people feel very tired (fatigued) during chemotherapy, particularly towards the end of treatment. This is a very common side effect and it is important to try to get as much rest as you need.

Gritty and sore eyes (conjunctivitis) This can happen because cytarabine can cause inflammation of the conjunctiva (the membrane that covers the white part of the eye and lines the eyelids). You will be given steroid eye drops to help prevent this side effect occurring. It is important to follow the instructions you are given.

Hair loss This usually starts 3–4 weeks after the first dose of chemotherapy, although it may occur earlier. Hair may be lost completely. You may also have thinning and loss of eyelashes, eyebrows and other body hair. Hair loss is temporary and your hair will start to grow again once the treatment ends. Your nurse can give you advice about coping with hair loss.

Irritation of stomach lining Methylprednisolone can lower the production of protective stomach mucus. This can irritate the lining of your stomach and may cause or aggravate an ulcer. To help reduce this effect, the methylprednisolone is usually given in injection form (intravenously). Tell your doctor if you have any indigestion, stomach pains or abdominal discomfort.

The levels of sugar in your blood may change While you are having steroids as part of the ESHAP regimen, your blood sugar levels may be checked with blood tests. You may be asked to test your urine for sugar. You will be shown how to do this.

People with diabetes should be more careful than usual when checking their blood sugar levels. You should contact your doctor if you have any problem controlling your diabetes. Also, tell your doctor if you get thirsty or if you are passing more urine than usual.

Diarrhoea This can usually be controlled easily with medicine, but tell your doctor if it is severe or if it continues. It is important to drink plenty of fluids if you do have diarrhoea. If you have any change in bowel habit, tell your doctor.

Ringing in your ears and hearing loss Cisplatin can cause some ringing in the ears (tinnitus). It can also cause some loss of ability to hear high-pitched sounds. This usually improves when the treatment is over. Tell your doctor if you notice any loss of hearing or ringing in your ears.

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. The problem usually improves slowly a few months after treatment is over.

Temporary taste alterations You may notice that your food tastes different. Your normal sense of taste will come back after the treatment finishes. A dietitian or specialist nurse at your hospital can give advice.

Loss of appetite A dietitian or specialist nurse at your hospital can give advice on boosting your appetite, coping with eating difficulties and maintaining weight.

Behavioural changes You may experience mood swings, difficulty with sleeping, and possibly anxiety or irritability. This can happen because of the steroids you are taking. Tell your doctor about any changes that are worrying you. Difficulty with sleeping may be helped by taking the steroids earlier in the day, but discuss this with your doctor first.

Skin changes You may develop an itchy rash. Your doctor can prescribe medicine to help with this. Rarely, your skin may darken, but it usually goes back to normal a few months after treatment.

During treatment, and for several months afterwards, you will be more sensitive to the sun and your skin may burn more easily. You can still go out in the sun, but always wear a high protection-factor suncream and cover up with clothes.

Risk of blood clots 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. However, most clots can usually be successfully treated by using drugs which thin the blood. Your doctor or nurse can give you more information.

Other medicines Some medicines can be harmful to take when you are having chemotherapy (including those you can buy in a shop or a chemist). Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Fertility Your ability to become pregnant or father a child may be affected by this treatment. It's important to discuss fertility with your doctor before starting treatment.

Contraception It's not advisable to become pregnant or father a child while taking this treatment, as it may harm the developing foetus. It is important to use effective contraception whilst taking this drug, and for some time afterwards. Again, discuss this with your doctor.

This section is based upon our ESHAP and R‑ESHAP chemotherapy factsheet which has been compiled using information from a number of reliable sources, including:

• Martindale: The Complete Drug Reference (35th edition). Eds. Sweetman et al. Pharmaceutical Press, 2007.
• Eshap – an Effective Chemotherapy Regimen in Refractory and Relapsing Lymphoma: A 4-year Follow-up Study. Velasques et al. J Clin Oncol. 1994.12 (6), 1169-76.
• British National Formulary (56th edition). British Medical Association and Royal Pharmaceutical Society of Great Britain, September 2008.
• The Chemotherapy Source Book (4th edition). Eds Perry et al, 2007.

For further references, please see general bibliography.