Methotrexate, cytarabine, thiotepa and rituximab (MATRix)

MATRix is the name of a cancer drug combination. It includes the drugs below. How to pronounce the drug names are in brackets.

• high dose methotrexate (meth-oh-trex-ate)
• high dose cytarabine (sye-ta-ra-bin)
• thiotepa (th-eye-oh-tee-pah)
• rituximab (ri-tuk-si-mab)

It is a treatment for a type of lymphoma called central nervous system lymphoma (CNS lymphoma).

How does MATRix work?

The brain is surrounded by a protective layer called the blood brain barrier. The drugs used in MATRix can pass through this into the brain and spinal cord.

Methotrexate, thiotepa and cytarabine are chemotherapy drugs. They work by destroying quickly dividing cells, such as cancer cells.

Rituximab is a type of targeted cancer drug called a monoclonal antibody. Rituximab targets a protein known as CD20, which is found on B cells. Rituximab attaches itself to all the CD20 proteins it finds. The cells of the immune system pick out the marked cells and kill them.

How do you have MATRix?

You have these drugs as a drip into your bloodstream (intravenously).

You usually 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

How often do you have MATRix?

You have MATRix as cycles of treatment. This means that you have the drugs and then a rest to allow your body to recover.

Each cycle of treatment lasts 21 days (3 weeks). You have up to 4 cycles. 

You usually stay in hospital overnight (inpatient) during your treatment and until your blood counts have recovered. How long you stay in hospital can vary from person to person.

Exactly how you have your drugs may depend on your circumstances. The following is an example:

Some people have an allergic reaction to rituximab. This can cause flu-like symptoms such as fever and sickness. To prevent an allergic reaction you usually have the first dose slowly over a few hours. You may also have paracetamol, steroids and an antihistamine drug before the treatment.

Folinic acid and G-CSF

You will have a drug called folinic acid 24 hours after starting methotrexate. It protects you against some of the side effects of methotrexate. You usually have it every 6 hours until your blood levels of methotrexate drop to a safe level. If your methotrexate levels are very high, you might have it every 3 hours.

You have a medicine called G-CSF after this treatment to help your white blood cells recover.

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). 

You might have a chest x-ray before you start your treatment.

What are the side effects of MATRix?

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:

Increased risk of getting an 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 weeing, 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. 

A serious reaction to an infection (sepsis)

Sepsis happens when your body has an overwhelming response to an infection. Symptoms include:

• Slurred speech or confusion
• Extreme shivering or muscle pain
• Passing no urine (in a day)
• Severe breathlessness
• It feels like you’re going to die  
• Skin mottled or discoloured

Allergic reaction

An allergic reaction that can cause a rash, shortness of breath, redness or swelling of the face and dizziness. Some allergic reactions can be life threatening. Alert your nurse or doctor if notice any of these symptoms.

Breathlessness and looking pale

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

Bruising, bleeding gums or nosebleeds

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 (known as petechiae).

Tiredness and weakness (fatigue) during and after treatment

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.

Headaches

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

Dizziness

This drug may make you feel drowsy or dizzy. Don’t drive or operate machinery if you have this.

Eye problems

You might have eye problems including blurred vision, sore, red, itchy, dry eyes (conjunctivitis), watery eyes, cataracts or an infection. Tell your healthcare team if you have any of these problems. 

You have steroid eye drops to try and prevent conjunctivitis during treatment.

Fits (seizures)

Tell your doctor if you have any fits, twitching or jerking of your limbs. 

Numbness and tingling

Numbness or tingling in fingers or toes is often temporary and can improve after you finish treatment. Tell your healthcare team if you're finding it difficult to walk or complete fiddly tasks such as doing up buttons. 

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.

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.

Sore mouth and throat

It may be painful to swallow drinks or food. Painkillers and mouth washes can help to reduce the soreness and keep your mouth healthy. 

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.

High blood sugar levels

You have regular blood and urine tests to check this. If you have diabetes you may need to check your blood sugar levels more often than usual. 

Skin problems

Skin problems include a skin rash, redness, itching and sensitivity to sunlight. This usually goes back to normal when your treatment finishes. Your healthcare team can tell you what products you can use on your skin to help.

Very rarely you could have a severe skin reaction that may 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 reaction is serious and could be life threatening.

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. 

Pain

You might get pain in your tummy, muscles, joints and back. Less commonly you may have pain in different areas of the body such as your mouth, ears, throat, bones, or chest.

Let your doctor or nurse know about any pain so that they can give you painkillers to help.

Call 999 straight away if you have pain in your chest.

Lung problems

You might develop a cough or breathing problems. This could be due to infection, such as pneumonia or inflammation of the lungs or airway. 

Lung problems can be serious. Let your doctor or nurse know straight away if you suddenly become breathless or develop a cough.

A less common side effect is fluid on the lung or scarring of the lungs. This also can cause breathlessness.

Kidney changes

You might have some changes in the way your kidneys work. You have regular blood tests to check how well they are working.

Liver problems

Your liver might become enlarged or a vein to the liver might get blocked. Tell your doctor or contact the advice line if you have any pain or discomfort on the right side where your liver is. 

You might have yellowing of the eyes and skin. This is called jaundice. It is caused by high levels of bile pigments in the blood. Let your doctor or nurse know straight away if you have this.

Rarely, you might have inflammation or scarring of the liver needing treatment.

Hearing changes

You might have some hearing loss, especially with high pitched sounds. You might also have some ringing in your ears (tinnitus). Tell your doctor or nurse if you notice any changes.

Changes in blood pressure

During treatment, your blood pressure may be lower or higher than normal. Tell your nurse if you feel dizzy, faint, or if you have headaches, nosebleeds, blurred or double vision, or shortness of breath. Your blood pressure usually goes back to normal while you are on treatment or when treatment ends.

Weight changes

You may gain weight while having this treatment. You may be able to control it with diet and exercise. Tell your healthcare team if you are finding it difficult to control your weight.

More rarely you might lose weight. 

Fluid build up

A build up of fluid may cause swelling in your arms, hands, ankles, legs, face and other parts of the body. Contact your healthcare team if this happens to you.

Inflammation around the drip site

Tell your nurse straight away if you have any pain, redness, swelling or leaking around your drip site.

Inflammation of the bladder (cystitis)

You might have pain when you pass urine. Or you may see blood when you pass urine. This is caused by inflammation of the bladder. Let your doctor know if this happens. 

You should drink 8 to 12 cups of fluid a day to try to prevent this. You will have fluid through a drip at certain points of your cycle of treatment too.

More rarely you might find that you find it more difficult to pee, or that you go less often. Or the treatment could cause damage to your kidneys.

Difficulty remembering things

You might have some difficulty remembering while having this treatment. Talk to your doctor or nurse if this happens.

Confusion, anxiety or depression

You or the people around you may notice that you feel confused. Or you might feel anxious or depressed. 

Rarely you might feel agitated or have hallucinations.

Tell your doctor or nurse if this happens.

Changes to the heart

You may have changes to the way your heart works. Your heart beat may be irregular. 

Less common side effects can be a very fast or slow heart beat and heart attack. A rare side effect can be inflammation of the heart muscle or the tissue surrounding the heart. 

Changes to periods and vaginal bleeding

Your periods might stop or you might have heavy bleeding from the vagina.

Indigestion

You might have some discomfort or gas after eating or drinking.

Changes in blood test results

There may be changes in levels of substances in the blood, such as amylase. More rarely there might be changes in your levels of calcium, potassium or phosphate. You will have regular blood tests to check the levels.

Inflammation of the bowel and food pipe (oesophagus) 

Inflammation of the bowel can cause abdominal pain, bloating or diarrhoea. Speak to your doctor if you have these symptoms.

Inflammation of the food pipe can cause a number of symptoms including feeling sick, taste changes, chest pain, bloating, burping and heartburn. Tell your doctor or nurse if you suddenly have any of these.

High temperature or chills

High temperature (fever, shivering or chills) can happen with this drug. This is because it can affect your body’s ability to control temperature. Having a fever with this drug doesn’t always mean you have an infection. But you should call your advice line, as an infection can be serious if not treated quickly.

Brain or nervous system problems

After treatment with high doses of cytarabine it is common to have one or more side effects affecting the brain or other parts of the nervous system. These might include personality changes or changes involving movement or speech. 

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:

• 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
• multi organ failure - a severe life threatening condition. Signs include feeling sick, passing less urine, swelling in arms and legs, chest pain, anxiety and confusion. Contact your doctor or call 999 straight away if you have any of these symptoms
• a weakness in a blood vessel in the brain (aneurysm). Call 999 if you have a sudden severe headache, stiff neck, sickness or sensitivity looking at light
• bleeding in the brain (stroke )
• slow movement of food through the bowel or a hole in your stomach or bowel (perforation). Contact your doctor straight away if you have pain, severe cramps, feeling tightness or bloating in the stomach area muscle weakness and loss of coordination. You might have reduced blood supply to the bowel
• inflammation of the pancreas (pancreatitis) – symptoms include severe tummy pain, feeling or being sick, a high temperature or you may have loose poo
• an increased risk of getting another type of cancer in the future
• difficulty falling asleep or staying sleeping (insomnia)
• stiffness in your muscles, arms or legs
• difficulty swallowing
• pain or ulcers around your back passage (anus)
• constipation
• a blocked, runny or itchy nose, or sneezing
• sweating and, or night sweats
• generally feeling unwell
• flushing - sudden reddening and warmth of the neck, upper chest and face
• high levels of uric acid in the blood
• shingles
• problems with your pituitary gland making hormones

Rare side effects

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

• changes to the way your blood clots - too little clotting causing bleeding or too much clotting causing blood clots
• a blood disorder where your red blood cells get destroyed faster than they can be made (haemolytic anaemia)
• a condition where your bone marrow stops making your blood cells (aplastic anaemia)
• skin ulcers
• weakening of the bones (osteoporosis)
• feeling like the room is spinning (vertigo)
• weakness on one side of your body
• swollen lymph nodes  
• swollen tummy (abdomen)
• changes to the levels of chemicals in your body caused by a breakdown of tumour cells (tumour lysis syndrome) - you will have regular blood tests to check for this
• taste changes
• redness, soreness and peeling of hands and soles of feet (palmar plantar syndrome)
• 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
• pain or ulcers around your vagina
• stomach ulcer
• changes to the colour of patches of your skin
• slow wound healing

Possible additional side effects from high dose cytarabine

There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include:

• inflammation of the lining of your peritoneum  causing symptoms such as tummy pain and a high fever
• breakdown of muscle tissue that happens very quickly. This can be serious. You might have extremely sore muscles or dark coloured wee (urine)

Other side effects

If you have side effects that aren't listed on this page, you can look at the individual drug pages:

• rituximab
• methotrexate
• cytarabine
• thiotepa

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do I 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.

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.

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. These may not be an option if you have to start treatment quickly. And these services are not available in every hospital, so you would need to ask your doctor about this.    

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.    

Breastfeeding 

Don’t breastfeed during this treatment or for 6 months afterwards. This is 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, yellow fever and one of the shingles vaccines called Zostavax.

You can 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 it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

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.