R-ESHAP

R-ESHAP is the name of a cancer drug combination. You have:

• R – rituximab (ri-tuk-si-mab)

• E – etoposide (ee-top-o-side)

• S – solu-medrone (sol-you-med-rone), you commonly hear it called methylprednisolone

• HA –high dose cytarabine (sye-ta-ra-bin), also known as Ara C

• P – cisplatin (sis-pla-tin)

It is a treatment for lymphoma. You usually have it before having a stem cell transplant, but you might have R-ESHAP if you’re not able to have a stem cell transplant.

How does R-ESHAP work?

Rituximab is a type of targeted cancer drug called a monoclonal antibody . It targets a protein called CD20 on the surface of the lymphoma cells. Rituximab sticks to all the CD20 proteins it finds. Then the cells of the immune system pick out the marked cells and kill them.

Etoposide, cisplatin and cytarabine are chemotherapy drugs. These drugs destroy quickly dividing cells, such as cancer cells.

Methylprednisolone is a type of steroid. It treats lymphoma by stopping the cancer cells growing and killing them. It may also help you feel less sick during treatment. And help reduce your body’s immune response, to try and prevent an allergic reaction to rituximab.

How do you have R-ESHAP?

You usually have all drugs as a drip into your bloodstream (intravenously). In some hospitals you might have methylprednisolone as a tablet.

Drugs into your bloodstream

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

Taking your tablets

You should take the right dose, not more or less.

Talk to your healthcare team before you stop taking a cancer drug, or if you miss a dose.

How often do you have R-ESHAP?

You usually have R-ESHAP as cycles of treatment. This means you have the drugs and then a rest to allow your body to recover.

Each cycle lasts 3 to 4 weeks. This depends on how quickly it takes for your blood count to recover.

If you’re having R-ESHAP before a stem cell cycle you usually have between 2 and 3 cycles of treatment. 

If you’re not having a stem cell transplant you might have up to 6 cycles of treatment.

Rituximab can cause an allergic reaction. So before each dose you have paracetamol, a steroid and an antihistamine drug such as chlorphenamine (Piriton).

For the first cycle of rituximab, you have it as a drip into your bloodstream slowly over a few hours. This is to prevent an allergic reaction. Your nurse will increase how fast it goes in (rate) approximately every 30 minutes if you have no allergic reaction.

Your next rituximab drip will usually go in quicker, but this will depend on how you got on with the first cycle.

When having R-ESHAP in the hospital (an inpatient), you have it slightly different from how you have it in the day care unit (an outpatient).

Below is an example of one way of having R-ESHAP:

Then you start the next treatment cycle.

You also have G-CSF. This is an injection under the skin (subcutaneous). It helps your body make white blood cells to lower your chance of getting an infection. You usually start this on day 6 and continue for up to 10 days.

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.

Before treatment starts you may have a blood test to check for viruses such as hepatitis B, hepatitis C, and HIV . This is called a viral screen.

It’s important for your doctor to know if you have had any of these viruses. This is because this treatment can weaken your immune system and can cause the virus to become active again (reactivation). 

What are the side effects of R-ESHAP?

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:

An allergic reaction 

A reaction may happen during the infusion. Symptoms can include a skin rash, itching, swelling of the lips, face or throat, breathing difficulties, fever and chills. Your nurse will give you medicines beforehand to try to prevent a reaction. 

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 a burning feeling when peeing, 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. 

Breathlessness 

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

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. This is known as petechiae.

Fatigue 

Tiredness and weakness (fatigue) can happen during and after treatment. Doing gentle exercises each day can keep your energy up. Don't push yourself, rest when you start to feel tired and ask others for help.

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. 

Eye changes 

You might have eye problems including blurred vision, sore, red, itchy, dry eyes or an infection.

Tell your doctor, nurse or pharmacist if you have this. You will have steroid eye drops to help prevent sore eyes.

Low levels of substances in your blood

You may have changes in levels of minerals and salts in your blood, such as low sodium. Other changes include low calcium levels, but this is less common. You might also have low levels of magnesium, but this is rare.

These levels usually go back to normal when you finish treatment. You have regular blood tests during treatment to check this.

Tummy (abdominal) pain 

Tell your treatment team if you have this. They can check the cause and give you medicine to help. 

Constipation 

Constipation is easier to sort out if you treat it early. Drink plenty and eat as much fresh fruit and vegetables as you can. Try to take gentle exercise, such as walking. Tell your healthcare team if you think you are constipated. They can give you a laxative if needed.

Liver changes 

You might have liver changes that are usually mild and unlikely to cause symptoms. These changes are usually picked up on blood tests. Let your healthcare team know if you are having the following symptoms: yellowing of the skin and white parts of the eyes; feeling or being sick; dark or tea coloured urine; pain in your tummy; rash and feeling tired and weak  .

You have regular blood tests to check for any changes in the way your liver is working.

Skin changes

You might notice skin changes, such as dryness, itching, rashes and your skin colour might become darker. Less commonly you may develop a break in the skin (ulcer) and peeling skin.

R-ESHAP can also cause a severe skin reaction, but this is rare. Symptoms usually 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

Tell your doctor or nurse if you have any of these symptoms so they can give you medicines to help.

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.

Loss of appetite 

You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Headaches 

Tell your healthcare team if you keep getting headaches. They can give you painkillers to help.

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.

Cytarabine syndrome

Cytarabine syndrome sometimes happens about 6 to 12 hours after having this drug. 

It causes a combination of symptoms. These include a high temperature, aching muscles, bone pain, occasionally chest pain, a rash, sore eyes, and extreme weakness. Steroids can help to prevent or treat this syndrome.

A build up of fluid in different parts of the body

A build up of fluid (oedema) may cause swelling in your arms, hands, ankles, legs, face, lungs and other parts of the body. 

Fluid on the lungs can cause symptoms such as difficulty in breathing especially when you lay down, cough, and you may cough up blood or bloody froth.

Contact your doctor or nurse if you notice any swelling or have changes to your breathing.

Feeling generally unwell

Speak to your doctor or nurse if you feel generally unwell after having this treatment.

High temperature or chills

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

Contact your advice line immediately if you have signs of infection, including a temperature of 37.5C or above. Or a temperature below 36C.

Low levels of an antibody called immunoglobulin G in your body

Immunoglobulin G is an antibody made by the immune system to fight bacteria and viruses. You have regular blood tests during and after treatment to check for this. 

Kidney damage 

To help prevent kidney damage, it is important to drink plenty of water. You might also have fluids into your vein before, during and after treatment. You have blood tests before your treatments to check how well your kidneys are working.

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:

• sepsis - a serious reaction to an infection. Signs can include feeling very unwell, not passing urine, a very high or very low temperature, shivering, slurred speech or confusion, breathlessness, mottled or discoloured skin, extreme shivering or muscle pain. Call 999 or go to accident and emergency (A&E) immediately if you have any of these symptoms
• low levels of calcium in your blood causing symptoms such as painful muscle spasms and cramps, twitching of muscles, numbness or tingling in feet and hands or around the mouth
• inflammation and ulcers in your anus
• sore mouth, throat and ulcers
• blood clots that can be life threatening; signs are pain, redness and swelling where the clot is. Feeling breathless can be a sign of a blood clot in the lung. Contact your advice line or doctor straight away if you have any of these symptoms
• unusual feelings (sensations) of the skin – such as numbness, tingling, pricking, burning, a creeping skin feeling, reduced sense of touch
• feeling agitated and anxious. Rarely it can cause you to feel very low in mood (depressed) or nervous
• indigestion symptoms include heartburn, bloating, and burping
• heart problems including changes to your heart rhythm. Contact your healthcare team straight away if you feel tightness in your chest, pain in your chest, feeling lightheaded, dizzy, pain in different parts of the body, sweating or anxious attack
• high blood pressure that might cause headaches, confusion, vision problems or chest pain
• numbness or tingling in fingers and toes that can make it difficult to do fiddly things such as doing up buttons
• changes to how well your kidneys are working- you will have regular blood tests to check for any changes 
• dizziness
• low blood pressure that can cause you to feel lightheaded or dizzy, sometimes this can happen when you stand up from sitting or lying down (orthostatic hypotension)
• redness, swelling and pain at the site of injection or drip
• difficulty sleeping or staying asleep (insomnia)
• high blood sugar levels- symptoms might include feeling very thirsty, a dry mouth, passing urine very often, feeling tired, blurred vision, weight loss, feeling or being sick, and fruity smelling breath
• weight loss
• sweating more than usual or night sweats
• pain in different parts of your body such as the where the cancer is, muscles, back and neck or ears
• you might have some hearing loss, especially with high pitched sounds. You might have ringing in the ears (tinnitus). Speak to your healthcare team about any changes
• inflammation of the food pipe – symptoms can include difficulty or pain when swallowing, heartburn, feeling as though food is stuck and bringing food or drink back up
• high levels of a substance (enzyme ) called LDH in the blood - you will have blood tests to check this
• a blocked, runny or itchy nose, or sneezing
• flushing - sudden reddening and warmth of the neck, upper chest and face
• several body parts (organs) stopping working
• difficulty swallowing
• sore throat
• lung problems such as breathlessness, chest pain, coughing, or tightening of the muscles that lines the airway (bronchospasm). Rarely you might have asthma or low levels of oxygen
• tense or tight muscles
• a second cancer such as leukaemia

Rare side effects

These side effects happen in fewer than 1 in 100 people (fewer than 1%). You might have one or more of them. They include:

• acute respiratory distress syndrome (ARDS) - cytarabine can cause ARDS due to inflammation of the lungs from infection or injury. It causes a lack of oxygen to your organs such as the lungs, heart and brain. You might have symptoms that include fast and shallow breathing, tiredness, drowsiness, confusion, feeling like you will faint and shortness of breath. ARDS is life threatening call 999 or get help straight away
• seizures (fits)
• problems with how your blood clots – too little clotting causing bleeding or too much clotting causing blood clots
• a condition where your bone marrow stops making your blood cells (aplastic anaemia)
• a blood disorder where your red blood cells get destroyed faster than they can be made (haemolytic anaemia)
• swollen lymph nodes
• taste changes
• a condition called cytokine release syndrome – when your immune system makes a large amount of cytokines . Symptoms include fever, chills, a headache, difficulty breathing, and dizziness
• inflammation of your blood vessels – symptoms can vary depending on which blood vessels are affected - general symptoms include feeling very tired, loss of appetite, weight loss, a high temperature, and aches and pains
• a hole in your stomach or bowel (perforation)
• changes to the levels of chemicals in your blood due to the breakdown of tumour cells (tumour lysis syndrome) – you have regular blood tests to check for this
• your kidneys may stop working – symptoms might include not passing enough pee, breathlessness, feeling tired and weak, confused, feeling sick, and you might have swelling on your legs, ankles and feet   
• changes in the brain that are usually reversible, causing a sudden onset of symptoms including headaches, dizziness, confusion, fits (seizures) and changes to your vision

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 drinks 

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.

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.    

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 with this drug and for at least a year afterwards.

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 6 months afterwards because the drugs may come through in your breast milk.

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, and yellow fever.

You can usually 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 a vaccine in relation to your cancer treatment.

Contact with others who have had immunisations 

You can be in contact with other people who have had live vaccines as injections. If someone has had a live vaccine by mouth or nasal spray there may be a small risk the vaccine virus can be passed onto you if your immune system is weakened.

Your healthcare team will let you know if you need to take any precautions if you are in close contact with someone who has had a live vaccine.

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.