Tucatinib, trastuzumab and capecitabine

Tucatinib, trastuzumab and capecitabine are cancer drugs. You can see below how to pronounce the drug names:

• tucatinib (too-ka-tinib)
• trastuzumab (tras-too-zoo-mab)
• capecitabine (ka-peh-site-a-been)

These drugs are a treatment for locally advanced or metastatic breast cancer. You might have this drug combination:

• if your cancer is HER2 positive
• after treatment with 2 or more anti HER2 treatments

How do tucatinib, trastuzumab and capecitabine work?

Tucatinib is a type of targeted drug called a tyrosine kinase inhibitor (TKI) . Tyrosine kinases are proteins that cells use to signal to each other to grow. They act as chemical messengers. Blocking these signals helps to slow or stop the cancer from growing.

There are several different tyrosine kinases. You have tests on your cancer cells before you have this treatment. The tests look for changes in these proteins or genes . With tucatinib they look for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) gene changes.

Trastuzumab is a type of targeted cancer drug called a monoclonal antibody . It works by attaching to HER2 so it stops the cancer cells from growing and dividing.

Capecitabine is a type of chemotherapy called an anti metabolite. The body changes capecitabine into a common chemotherapy drug called fluorouracil. It stops cells from making and repairing DNA . Cancer cells need to make and repair DNA so they can grow and multiply.

How do you have tucatinib, trastuzumab and capecitabine?

You take tucatinib and capecitabine as tablets that you swallow. You swallow the tablets whole with a glass of water. You take tucatinib with or without a meal. You take capecitabine within 30 minutes after the end of a meal.

You have trastuzumab as an injection under the skin (subcutaneously).

Taking your tablets

Speak to your pharmacist if you have problems swallowing the tablets.

Whether you have a full or an empty stomach can affect how much of a drug gets into your bloodstream.

You should take the right dose, no more or less.

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

Injection under your skin (subcutaneous injection)

You usually have injections under the skin (subcutaneous injection) into the stomach, thigh or top of your arm.

You might have stinging or a dull ache for a short time after this type of injection but they don't usually hurt much. The skin in the area may go red and itchy for a while.

How often do you have tucatinib, trastuzumab and capecitabine?

You have tucatinib, trastuzumab and capecitabine as cycles of treatment. This means you have the drugs and then a rest to allow your body to recover.

Each cycle of treatment lasts 21 days (3 weeks). You usually keep taking tucatinib, trastuzumab and capecitabine for as long as they work or until the side effects get too bad.

You have each cycle of treatment in the following way:

You then start the next cycle of treatment.

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.

You will also have tests to check how well your heart works.

DPD deficiency

Before starting treatment with capecitabine you have a blood test to check levels of an enzyme called dihydropyrimidine dehydrogenase (DPD). A low DPD level means you are more likely to have severe side effects from these drugs. So you may start treatment with a lower amount (dose) of the drug or have a different treatment. Your doctor, pharmacist or nurse will talk to you about this.

What are the side effects of tucatinib, trastuzumab and capecitabine?

Side effects can vary from person to person. They also depend on what other treatment you are having. 

When to contact your team

Your doctor, pharmacist or nurse will go through the possible side effects. They will monitor you closely 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

• the side effects are affecting your daily life

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 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 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. 

Less commonly, you might get sepsis. This is a serious reaction to an infection. Signs can include feeling very unwell, not passing urine, being sick, having a very high or very low temperature or shivering. Contact your advice line straight away if you have 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 nose bleeds

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).

Less commonly, you might have bleeding from your small bowel, stomach, food pipe (oesophagus) or bottom (rectum). Symptoms might include tummy pain, vomiting blood, having dark stools or blood in your stool. Contact 999 or your healthcare team immediately if you have this.

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.

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.

A sore mouth

You might get a sore mouth and mouth ulcers. It may be painful to swallow drinks or food. You will have mouth washes to keep your mouth healthy.

You can have painkillers to reduce the soreness. Take them half an hour before meals to make eating easier.

Less commonly, you might have a painful burning or tingling sensation in your mouth, or you might have no sensation.

Skin changes

You might notice skin changes, such as dryness, itching and a rash similar to acne. Other skin changes include flat or raised areas, red bumps with pus inside, red raised areas all over your body or a reaction that causes redness on the palms of your hands or soles of your feet.

Less commonly, your skin might look bruised, you might sweat a lot, have night sweats or have hives.

Tell your doctor if you have any rashes or itching. Don't go swimming if you have a rash because the chlorine in the water can make it worse.

If your skin gets dry or itchy, using unperfumed moisturising cream may help. Check with your doctor or nurse before using any creams or lotions. Wear a high factor sunblock if you’re going out in the sun.

Pain in your joints, muscles or other parts of the body

You might feel some pain in your muscles and joints. Your muscles might also feel tight. Pain might also include chest pain.

Contact your doctor or nurse as soon as possible if you have any chest pain.

Less commonly, you might have pain in your back, bones, jaw, neck or arms and legs. Or you might have muscle spasms or a locked jaw.

Speak to your doctor or nurse about what painkillers you can take to help with this.

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working.

Less commonly, you might have inflammation of the liver (hepatitis) or tenderness of the liver.

Rarely, your skin or the white of your eyes may turn yellow (jaundiced).

Weight loss

You might lose weight while having this treatment. Let your doctor or nurse know and they can recommend ways of maintaining your weight. Or they can refer you to a dietitian.

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.

Difficulty sleeping or feeling drowsy

If you have difficulty sleeping, it can help to change a few things about how you try to sleep. Try to go to bed and get up at the same time each day and spend some time relaxing before you go to bed. Some light exercise each day may also help. 

Less commonly, you might feel drowsy and sleepy.

Shaky hands (tremor)

You may develop shaky hands (tremor) with this treatment.

Dizziness

This drug might make you feel dizzy. You might also feel dizzy when standing or moving around. Or it might feel like the world is spinning.

Don’t drive or operate machinery if you have this.

Headaches

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

Nerve changes

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. 

Other nerve changes may include an unpleasant feeling when being touched, weakness in your hands, arms or feet or nerve pain.

Less commonly, nerve changes might cause stiff muscles. 

Taste changes

Taste changes may make you go off certain foods and drinks. You may also find that some foods taste different from usual or that you prefer to eat spicier foods. Your taste gradually returns to normal a few weeks after your treatment finishes.

Eye changes

You might have eye problems such as redness and inflammation of the thin layer of tissue that covers the front of the eye (conjunctivitis). Or you might have increased production of tears.

Less commonly, you might have dry eyes, eye pain, blurred vision or loss of vision.

Let your doctor or nurse know if you have any problems with your eyes. They can give you eye drops to help.

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.

Less commonly, a sudden severe increase in blood pressure might happen.

Heart changes

You may have changes to how your heart works, such as your heart rhythm. Tests such as a heart trace (ECG) might pick this up. Or your heart muscle might not pump blood as well as it should (heart failure). Symptoms might include breathlessness or tiredness.

Less commonly, a heart attack might happen. Symptoms of a heart attack include an overwhelming pain in the chest that might feel heavy, tight or as though it's squeezing the chest. Other heart attack symptoms include feeling lightheaded, dizzy, pain in different parts of the body, sweating or anxiety.                                    

Hot flushes

We have some tips for coping with hot flushes in women and hot flushes in men. This information also includes some of the possible treatments. Talk to your doctor if your hot flushes are hard to cope with. They might be able to prescribe some medicines to help.

Lung changes

This treatment can cause lung problems.

Let your doctor or nurse know straight away if you suddenly become breathless or develop a cough.

Less commonly, you might have lung changes such as inflammation caused by an infection, asthma or fluid collecting between the layers covering the lung.

Rarely, you might have lung inflammation not caused by an infection or wheezing when breathing.

Runny nose

You might have a runny nose while having treatment.

Swollen lips

You may develop swollen lips with this treatment.

Tummy (abdominal) pain

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

Indigestion or heartburn

Contact your doctor or pharmacist if you have indigestion or heartburn. They can prescribe medicines to help.

Less commonly, you might feel bloated or have tummy discomfort.

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.

Hair loss

The hair on your head could become thinner or you may gradually lose your hair. 

Your hair will grow back once treatment has finished. But it is likely to be softer. And it may grow back a different colour or be curlier than before. 

Nail changes

You might have nail problems that include broken nails. Tell your doctor or nurse if this happens.

Soreness, redness and peeling on palms and soles of feet

The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome.

Moisturise your skin regularly. Your healthcare team will tell you what moisturiser to use.

Tiredness and weakness

You might feel very tired and as though you lack energy.

Various things can help you to reduce tiredness and cope with it, for example exercise. Some research has shown that taking gentle exercise can give you more energy. It is important to balance exercise with resting.

Flu-like symptoms

You might have flu-like symptoms such as fever, chills and muscle aches.

Contact your advice line if you have flu-like symptoms and check if you can take paracetamol.

Allergic reaction

A reaction may happen during the injection. Symptoms can include pain at the injection site, a skin rash, itching, red skin, breathing difficulties or a cough. You might also have a drop in blood pressure causing dizziness or a fast heart rate. Your nurse will give you medicines beforehand to try to prevent a reaction.

Rarely, an allergic reaction can be severe and life threatening.

Tell your doctor or nurse immediately if at any time you feel unwell. They will give you medicine to help relieve your symptoms.

Swelling in the face, hands and feet

This usually goes away on its own, but tell your doctor or nurse if you have it.

Blood clots

Blood clots can develop in the deep veins of your body, usually the leg. This is called deep vein thrombosis (DVT). A blood clot can be very serious if it travels to your lungs (pulmonary embolism), although this isn’t common.

Symptoms of a blood clot include:

•    pain, redness and swelling around the area where the clot is and may feel warm to touch
•    breathlessness
•    pain in your chest or upper back – dial 999 if you have chest pain
•    coughing up blood

Sore throat

Your throat might get sore. Or you might have an unpleasant sensation when swallowing. It may be painful to swallow drinks or food. You can have painkillers to reduce the soreness. Take them half an hour before meals to make eating easier.

Tell your doctor or nurse if your throat is sore.

Inability to balance temperature

Your body might have difficulty balancing your temperature between cold and hot.

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:

• feeling overly worried (anxious) or low in mood (depression)
• feeling generally unwell
• enlarged blood vessels inside or around the bottom (piles). Your doctor can prescribe creams to help relieve discomfort
• a dry mouth
• changes to how your kidneys work. You might have blood or protein in your urine. You will have regular tests to check this
• breast inflammation or infection
• bruises
• low levels of substances in the blood such as potassium, sodium, magnesium and calcium. You will have regular blood tests to check your levels
• high blood sugar levels. Symptoms include headaches, feeling thirsty and blurred vision. You have regular tests to check your blood sugar levels. You may need to check your levels more often if you are diabetic
• a ringing sound in your ears (tinnitus) or hearing loss. Rarely, you might have complete hearing loss
• sudden reddening and warmth of the neck, upper chest and face (flushing)
• inflammation of a vein
• hiccups
• hoarseness
• difficulty swallowing
• discomfort or pain when passing urine

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:

• fluid collecting between the layers covering the heart (pericardial effusion). Symptoms include shortness of breath or chest pain
• kidneys stopping working

Other side effects

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:

• a cancerous or non cancerous (benign) tumour growing
• high uric acid levels in the blood due to the breakdown of tumour cells (tumour lysis syndrome) – you will have regular blood tests to check this
• high levels of substances in the blood, such as potassium. Symptoms include heart palpitations, shortness of breath, chest pain, nausea, or vomiting. You have regular blood tests to check this
• swelling of a part of the eye called the optic disc due to increased pressure in the skull (papilloedema). Symptoms include headaches, feeling and being sick and vision changes such as blurred or double vision. Contact your healthcare team immediately if you have these symptoms
• the heart not pumping enough blood and oxygen to the brain and other organs (cardiogenic shock). Symptoms include confusion, sweating, and rapid breathing
• lung changes such as scarring of the lung tissue, too much fluid in the lung, tightening of the muscles of the airway or swelling of the voice box. This can cause breathing problems which can be life threatening due to a lack of oxygen to important organs
• pregnancy changes such as too little amniotic fluid around the baby or the baby’s kidneys and lungs not developing properly

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, food and drink

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 father a child while you are having treatment with this drug and for at least 7 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment. Let them know immediately if you or your partner falls pregnant while undergoing treatment.

Loss of fertility

It is not known whether this treatment affects fertility in people. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Breastfeeding

Don’t breastfeed during this treatment and for 7 months afterwards. The drugs may come through in the breast milk.

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 about this treatment

For further information about this treatment and possible side effects go to the electronic Medicines Compendium (eMC) website. You can find the patient information leaflet 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.