What is hyper-CVAD?

Hyper-CVAD is used to treat some types of non-Hodgkin lymphoma (NHL) and acute lympho-blastic leukaemia (ALL). It is best to read this information with our general information about chemotherapy and the type of cancer you have.

Hyper is short for hyperfractionated. It means you are given more than one treatment of the same drug in a day. CVAD stands for the initials of some of the drugs used

Hyper-CVAD treatment also includes two other chemotherapy drugs:

Because of this, it is sometimes called hyper-CVAD/MTX-cytarabine. But most people call it hyper-CVAD. Hyper-CVAD is sometimes given with a targeted therapy called rituximab. This treatment is called R-hyper-CVAD.

Your doctor will talk to you about this treatment and its possible side effects before you agree (consent) to have treatment.

How hyper-CVAD is given

You will be given hyper-CVAD during a stay in hospital or in the chemotherapy day unit. A chemotherapy nurse will give it to you.

During treatment, you usually see a cancer doctor, a blood specialist (haematologist), a chemo-therapy nurse or a specialist nurse and a specialist pharmacist. This is who we mean when we mention doctor or nurse in this information.

Before or on the day of treatment, a nurse or person trained to take blood (phlebotomist) will take a blood sample from you. This is to check that your blood cells are at a safe level to have chemotherapy.

You will see a doctor or nurse before you have chemotherapy. They will ask you how you have been feeling. If your blood results are okay, the pharmacist will prepare your chemotherapy. Your nurse will tell you when your treatment is likely to be ready.

Your nurse usually gives you anti-sickness (anti-emetic) drugs before the chemotherapy.

The chemotherapy drugs can be given through:

  • a short thin tube the nurse puts into a vein in your arm or hand (cannula)
  • a fine tube that goes under the skin of your chest and into a vein close by (central line)
  • a fine tube that is put into a vein in your arm and goes up into a vein in your chest (PICC line).

The nurse will give you the different chemotherapy drugs into your line separately.

  • Cyclophosphamide is given as a drip over 2 hours.
  • Vincristine is given as a drip over 10 minutes.
  • Doxorubicin (a red fluid) is given as a drip (how long it is given over may depend on the hospital).
  • Dexamethasone is given as tablets or an injection into your line.

Methotrexate and cytarabine are given on a different day from the other chemotherapy drugs:

  • Methotrexate is given as a drip over 24 hours.
  • Cytarabine is given as a drip that lasts 2 hours.

Sometimes methotrexate and cytarabine are given by injection into the fluid around the spinal cord (intrathecally).

Your course of hyper-CVAD

You have chemotherapy as a course of several sessions (cycles) of treatment over a few months. With hyper-CVAD, you have two different schedules of treatment called A and B. You will have each schedule four times in a pattern of A then B. Each cycle of hyper-CVAD lasts 21 days.

But if you have hyper-CVAD before a stem cell transplant, you usually only have 2 cycles of each schedule.

Schedule A (cycles 1, 3, 5 and 7)

Day 1 – your nurse gives you 2 separate drips of cyclophosphamide. The second drip is given 12 hours after the first. You will have fluids through a drip before and after cyclophosphamide. You may also have a drug called mesna (Uromitexan®) to prevent bladder irritation.

You also start taking dexamethasone (steroid) tablets. You take them for 4 days (days 1-4).

Day 2 – you have 2 drips of cyclophosphamide again. They are given 12 hours apart.

Day 3 – you have the cyclophosphamide treatment again.

Day 4 – you have vincristine and doxorubicin as a drip. You can usually go home the day after it finishes.

Days 5 to 10 – you do not have any treatment.

Day 11 – you have vincristine again, usually in the chemotherapy day unit. You also start taking dexamethasone tablets for 4 days (days 11 to 14).

Days 15 to 21 – you do not have any treatment. This is the last week in the cycle. Your next cycle will be Schedule B.

Schedule B (cycles 2, 4, 6 and 8)

Day 1 – you nurse gives you methotrexate as a drip.

Day 2 – you usually have a drug called leucovorin (folinic acid) as a drip. This helps to reduce the side effects of methotrexate. You have it regularly until the methotrexate is out of your system. You also have 2 drips of cytarabine. They are given 12 hours apart.

Day 3 – you have 2 more drips of cytarabine. You can usually go home after this if your methotrexate levels are okay.

Days 4 to 21 – you do not have any treatment. This completes the cycle of hyper-CVAD. Your next cycle will be schedule A again.

Chemotherapy by injection into the spinal fluid

Some people have methotrexate and cytarabine given into the spinal fluid. This is called intrathecal chemotherapy. Your cancer doctor or nurse will tell you more about this. You usually have it on different days from the rest of your chemotherapy treatment.

The doctor numbs an area of skin over your spine with local anaesthetic. They gently insert a needle between two of the spinal bones. This is called a lumbar puncture. They inject the chemotherapy drug through this needle into the spinal fluid.

You need to lie flat for a while afterwards.

Going home

Before you go home, the nurse or pharmacist will give you anti-sickness drugs to take. You may also be given other drugs to take, for example to help reduce your risk of getting an infection. Take all your tablets exactly as they have explained to you.

About side effects

We explain the most common side effects of this treatment here. We also include some less common side effects.

You may get some of the side effects we mention, but you are unlikely to get all of them. If you are also having treatment with other cancer drugs, you may have some side effects that we have not listed here. Always tell your doctor, nurse or pharmacist about any side effects you have.

Your doctor can give you drugs to help control some side effects. It is important to take them exactly as your nurse or pharmacist explains. This means they will be more likely to work for you. Your nurse will give you advice about managing your side effects. After your treatment is over, most side effects start to improve.

Serious and life-threatening side effects

Some cancer treatments can cause severe side effects. Rarely, these may be life-threatening. Your cancer doctor or nurse can explain the risk of these side effects to you.

Contact the hospital

Your nurse will give you telephone numbers for the hospital. If you feel unwell or need advice, you can call them at any time of the day or night. Save these numbers in your phone or keep them somewhere safe.

More information

We cannot list every side effect for this treatment. There are some rare side effects that are not listed. You can visit the electronic Medicines Compendium (eMC) for more detailed information.

Side effects while treatment is being given

Some people may have side effects while they are being given the chemotherapy or shortly after they have it:

Allergic reaction

Some people have an allergic reaction while having this treatment.

Signs of a reaction can include:

  • feeling hot or flushed
  • a skin rash
  • itching
  • shivering
  • feeling dizzy
  • a headache
  • feeling breathless
  • swelling of your face or mouth
  • pain in your back, tummy or chest.

Your nurse will check you for signs of a reaction during your treatment. If you feel unwell or have any of these signs, tell them straight away. If you do have a reaction, it can be treated quickly.

Sometimes a reaction can happen up to 24 hours after treatment. If you get any signs or feel unwell after you get home, contact the hospital straight away.

The drug leaks outside the vein

If the drug leaks outside the vein, it can damage the surrounding tissue. This is called extravasation. Extravasation is not common but if it happens it is important to treat it quickly. Tell your nurse straight away if you have any stinging, pain, redness or swelling around the vein.

If you get any of these symptoms after you get home, contact the doctor or nurse straight away on the contact telephone number they gave you.

Facial flushing

You may suddenly feel warm and your face may get red while the drug is being given. This should only last a few minutes.

Flushes and blocked nose

Some people may have hot flushes, a feeling of having a blocked nose and a strange taste in their mouth when cyclophosphamide is given.

This does not last for long. But if you notice this, tell your nurse. They can give the treatment more slowly, which will reduce these symptoms.

Common side effects

Risk of infection

This treatment can reduce the number of white blood cells in your blood. These cells fight infection. If the number of white blood cells is low, you are more likely to get an infection. A low white blood cell count is called neutropenia.

If you have an infection, it is important to treat it as soon as possible. Contact the hospital straight away on the 24-hour contact number you have if:

  • your temperature goes over 37.5°C (99.5°F)
  • you suddenly feel unwell, even with a normal temperature
  • you have symptoms of an infection.

Symptoms of an infection include:

  • feeling shivery
  • a sore throat
  • a cough
  • diarrhoea
  • needing to pass urine often.

It is important to follow any specific advice your cancer treatment team gives you.

The number of white blood cells will usually return to normal before your next treatment. You will have a blood test before having more treatment. If your white blood cell count is low, your doctor may delay your treatment for a short time.

G-CSF (granulocyte-colony stimulating factor) is a type of drug called a growth factor. It encourages the body to make more white blood cells.

Your doctor may give you G-CSF:

  • if the number of white blood cells is very low
  • to stop the number of white blood cells getting low.

You have it as a small injection under the skin.

Bruising and bleeding

This treatment can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot. 

Tell your doctor if you have any bruising or bleeding that you cannot explain. This includes:

  • nosebleeds
  • bleeding gums
  • tiny red or purple spots on the skin that may look like a rash.

Some people may need a drip to give them extra platelets. This is called a platelet transfusion.

Anaemia (low number of red blood cells)

This treatment can reduce the number of red blood cells in your blood. These cells carry oxygen around the body. If the number of red blood cells is low, you may be tired and breathless. Tell your doctor or nurse if you feel like this. If you are very anaemic, you may need a drip to give you extra red blood cells. This is called a blood transfusion.

Feeling sick

You may feel sick during this treatment. Your doctor will give you anti-sickness drugs to help prevent or control sickness. Take the drugs exactly as your nurse or pharmacist tells you. It is easier to prevent sickness than to treat it after it has started.

If you feel sick, take small sips of fluids and eat small amounts often. If you continue to feel sick, or if you vomit more than once in 24 hours, contact the hospital straight away. They will give you advice and may change the anti-sickness drug to one that works better for you.

Tiredness

Feeling tired is a common side effect. Try to pace yourself and plan your day so you have time to rest. Gentle exercise, like short walks, can give you more energy. If you feel sleepy, do not drive or operate machinery.

Hair loss

Your hair will get thinner or you may lose all the hair from your head. You may also lose your eyelashes, eyebrows or other body hair. Hair loss usually starts after your first or second treatment.

Your nurse can talk to you about ways to cope with hair loss. There are ways to cover up hair loss if you want to. It is important to cover your head to protect your scalp when you are out in the sun.

Hair loss is almost always temporary and your hair will usually grow back after treatment ends.

Sore mouth

You may get a sore mouth or mouth ulcers. This can make you more likely to get a mouth infection.

Use a soft toothbrush to clean your teeth or dentures in the morning, at night and after meals.

If your mouth is sore:

  • tell your nurse or doctor – they can give you a mouthwash or medicines to help
  • try to drink plenty of fluids
  • avoid alcohol, tobacco, and foods that irritate your mouth.

Changes to your taste

You may get a bitter or metal taste in your mouth. Sucking sugar-free sweets may help with this. Some foods may taste different or have no taste. Try different foods to find out what tastes best to you. Taste changes usually get better after treatment finishes. Your nurse can give you more advice.

Diarrhoea

This treatment may cause severe diarrhoea. Diarrhoea means passing more stools (poo) than is usual for you, or having watery or loose stools. If you have a stoma, it will be more active than usual.

Your hospital team may give you anti-diarrhoea drugs to take at home.

If you have diarrhoea or a mild increase in stoma activity:

  • follow any advice from your cancer team about taking anti-diarrhoea drugs
  • drink at least 2 litres (3½ pints) of fluids each day
  • avoid alcohol, caffeine, milk products, high-fat foods and high-fibre foods.

Contact the hospital straight away if:

  • you have diarrhoea at night
  • you have diarrhoea more than 4 times in a day
  • you have a moderate or severe increase in stoma activity
  • the anti-diarrhoea drugs do not work within 24 hours.

You may need to go to hospital to have fluids through a drip.

Constipation

This treatment can cause constipation. Here are some tips that may help:

  • Drink at least 2 litres (3½ pints) of fluids each day.
  • Eat high-fibre foods, such as fruit, vegetables and wholemeal bread.
  • Do regular gentle exercise, like going for short walks.

If you have constipation, contact the hospital for advice. Your doctor can give you drugs called laxatives to help.

Discoloured urine

Doxorubicin may make your urine a pink-red colour for up to 48 hours after you have had your treatment.

Bladder irritation

Cyclophosphamide may irritate your bladder and cause discomfort when you pass urine. Make sure you drink plenty of fluids during the 24 hours following chemotherapy. Try to drink at least 2 litres (3½ pints).

It is also important to empty your bladder regularly and to try to pass urine as soon as you feel the need to go.

If you are treated with higher doses of cyclophosphamide, you will be given fluids through a drip (infusion). You may also be given a drug called mesna (Uromitexan®) through a drip or tablets. This helps to prevent bladder irritation.

Contact the hospital straight away if you feel any discomfort or stinging when you pass urine, or if you notice any blood in it.

Tummy pain or indigestion

Steroids can irritate the stomach lining. Tell your doctor or nurse if you have pain in your tummy (abdomen) or indigestion. They can give you drugs to help reduce stomach irritation. Take your tablets with food to help protect your stomach.

Raised blood sugar levels

Steroids can raise your blood sugar levels. Your nurse will check your blood sugar regularly for this. They may also test your urine for sugar. Symptoms of raised blood sugar include:

  • feeling thirsty
  • needing to pass urine often
  • feeling tired.

Tell your doctor or nurse if you have these symptoms.

If you have diabetes, your blood sugar levels may be higher than usual. Your doctor will talk to you about how to manage this. You may need to adjust your insulin or tablet dose.

Increased appetite

Steroids can make you feel more hungry than usual and you may gain weight. Your appetite will go back to normal when you stop taking them. If you are worried about gaining weight, talk to your doctor or nurse.

Skin changes

Hyper-CVAD may affect your skin. Your doctor or nurse can tell you what to expect. If your skin feels dry, try using an unperfumed moisturising cream every day. Hyper-CVAD can cause a rash, which may be itchy.

During, and for some months after treatment, you will be more sensitive to the sun. This means that your skin may burn more easily. Cover up with clothing and a hat. Use a sun cream with a sun protection factor (SPF) of at least 30 and at least four or five UVA stars. Your skin may darken. But it will return to its normal colour after you finish treatment. If you have had radiotherapy, the area that was treated may become red or sore.

Always tell your doctor or nurse about any skin changes. They can give you advice and may give you creams or medicines to help. Any changes to your skin are usually temporary and improve when treatment finishes.

Nail changes

Your nails may grow more slowly or break more easily. You may notice white lines across your nails, or other changes to their shape or colour. Once the treatment has ended, any changes usually take a few months to grow out.

There are things you can do to look after your nails:

  • Keep your nails and hands moisturised.
  • Wear gloves to protect your nails when you are doing things in the house or garden.
  • Do not use false nails during this treatment. It is fine to wear nail varnish.
  • If your toenails are affected, wear well-fitted shoes to cushion them.

Numb or tingling hands or feet (peripheral neuropathy)

This treatment affects the nerves, which can cause numb, tingling or painful hands or feet. You may find it hard to fasten buttons or do other fiddly tasks.

Tell your doctor if you have these symptoms. They sometimes need to lower the dose of the drug. The symptoms usually improve slowly after treatment finishes, but for some people they may never go away. Talk to your doctor if you are worried about this.

Build-up of fluid

Steroids may cause your ankles and legs to swell. This is because of fluid building up. Tell your doctor or nurse if fluid builds up. If your ankles and legs swell, it can help to put your legs up on a foot stool or cushion. The swelling gets better after the treatment ends.

Eye problems

This treatment may make your eyes feel sore, red and itchy (conjunctivitis). Your doctor will prescribe eye drops to help prevent this. It is important to use these as you are told to.

This treatment may also make your eyes more sensitive to light and cause blurry vision. If you have pain or notice any change in your vision, always tell your doctor or nurse.

Effects on the kidneys

This treatment can affect how your kidneys work. This is usually mild and goes back to normal after treatment. You will have blood tests to check how well your kidneys are working.

It is important to drink at least 2 litres (3½ pints) of fluids each day to help protect your kidneys.

Changes in the way the liver works

Hyper-CVAD may affect how your liver works. This is usually mild and goes back to normal after treatment. You will have blood tests to check how well your liver is working.

Raised levels of uric acid (tumour lysis syndrome)

This treatment may cause the cancer cells to break down quickly. This releases uric acid (a waste product) into the blood. The kidneys usually get rid of uric acid, but may not be able to cope with large amounts. Too much uric acid can cause swelling and pain in the joints, which is called gout.

Your doctor may give you drugs to help prevent this. Drinking at least 2 litres (3 ½ pints) of fluid a day will also help. You will have regular blood tests to check the uric acid levels.

Mood and behaviour changes

Steroids can affect your mood. You may feel anxious or restless, and have mood swings or problems sleeping. Taking your steroids in the morning may help you sleep better at night.

If you have any of these side effects, tell your doctor or nurse. They may make some changes to your treatment. It is best not to drive or operate machinery if you feel like this.

Less common side effects

Soreness and redness of palms of hands and soles of feet

This is called palmar-plantar or hand-foot syndrome. Your doctor or nurse can give you advice and prescribe creams to improve the symptoms. It can help to keep your hands and feet cool and to avoid tight-fitting socks, shoes and gloves. It will start to get better when treatment ends.

Effects on the lungs

This treatment can cause changes to the lungs. Tell your doctor if you develop:

  • a cough
  • wheezing
  • a fever (high temperature)
  • breathlessness.

You should also tell them if any existing breathing problems get worse. You may have tests to check your lungs.

Effects on the heart

Chemotherapy can affect the way the heart works. You may have tests to see how well your heart is working. These may be done before, during and sometimes after treatment. If the treatment is causing heart problems, your doctor can change the type of chemotherapy you are having.

Contact a doctor straight away if you:

  • have pain or tightness in your chest
  • feel breathless or dizzy
  • feel your heart is beating too fast or too slowly.

Other conditions can cause these symptoms, but it is important to get them checked by a doctor.

Effects on the nervous system

Rarely, hyper-CVAD can affect the nervous system. Tell your doctor or nurse straight away if you notice that you feel:

  • drowsy
  • confused
  • dizzy
  • unsteady.

It is important not to drive or operate machinery if you notice these effects.

Rarely, hyper-CVAD can cause seizures (fits). Your doctor or nurse will explain more about this.

Side effects of intrathecal hyper-CVAD

The side effects of intrathecal hyper-CVAD may be different from those mentioned here. Your doctor or nurse will talk to you about this.

When methotrexate is given this way, it can cause:

  • headaches
  • dizziness
  • tiredness
  • blurred vision
  • loss of balance for a few hours.

Tell your nurse or doctor straight away if you have any of these.

It is important to tell your doctor or nurse straight away if you feel ill or have severe side effects. This includes any we do not mention here.

Other information

Blood clot risk

Cancer and some cancer treatments can increase the risk of a blood clot. Symptoms of a blood clot include:

  • pain, redness or swelling in a leg or arm
  • breathlessness
  • chest pain.

If you have any of these symptoms, contact a doctor straight away.

A blood clot is serious, but can be treated with drugs that thin the blood. Your doctor or nurse can give you more information.

Other medicines and food

Some medicines can affect chemotherapy or be harmful when you are having it. This includes medicines you can buy in a shop or chemist. Tell your cancer doctor about any medicines you are taking, including vitamins, herbal drugs and complementary therapies.

It is important to avoid eating grapefruit or drinking grapefruit juice during your course of chemotherapy. This is because a chemical in grapefruit can affect how well the treatment works or can make side effects worse.

Vaccinations

Your doctor or nurse may talk to you about vaccinations. These help reduce your risk of getting infections.

Doctors usually recommend that you have a flu jab, which is an inactivated vaccination. People with weak immune systems can have this type of vaccination.

If your immune system is weak, you need to avoid live vaccinations such as shingles. Your cancer doctor or GP can tell you more about live vaccinations.

Contraception

Your doctor will advise you not to:

  • get pregnant while having this treatment and for at least 1 year afterwards
  • make someone pregnant while having this treatment and for at least 6 months afterwards.

This is because the drugs may harm the developing baby. It is important to use effective contraception.

Breastfeeding

Women are advised not to breastfeed while having this treatment. This is because the drugs could be passed to the baby through breast milk.

Fertility

Some cancer drugs can affect whether you can get pregnant or make someone pregnant.

If you are a woman, your periods may become irregular or stop. This may be temporary, but for some women it is permanent. Your menopause may start sooner than it would have done.

There may be ways to preserve fertility for men and women. If you are worried about fertility, it is important to talk with your doctor before you start treatment.

Sex

If you have sex in the first few days after chemotherapy, you need to use a condom. This is to protect your partner in case there is any chemotherapy in semen or vaginal fluids.

Medical and dental treatment

If you need medical treatment for any reason other than cancer, always tell the doctors and nurses that you are having cancer treatment. Give them the contact details for your cancer doctor so they can ask for advice.

If you think you need dental treatment, talk to your cancer doctor or nurse. Always tell your dentist you are having cancer treatment.