This information is about a chemotherapy treatment called Hyper-CVAD, which is used to treat some types of non-Hodgkin lymphoma and acute lymphoblastic leukaemia (ALL).
You will see your doctor regularly while you have this treatment so they can monitor the effects of the chemotherapy.
The drugs that are used
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Hyper-CVAD is named after the initials of the chemotherapy drugs used:
Hyper is short for hyperfractionated, which means that more than one treatment (or dose) of the same drug is given in a day.
Hyper-CVAD treatment also includes another two drugs, called methotrexate and cytarabine, that alternate with the above drugs. For this reason, the treatment is sometimes called Hyper-CVAD/MTX-Cytarabine, but this is more commonly abbreviated to Hyper-CVAD.
How treatment is given
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Hyper-CVAD will be given to you while you are in hospital. The treatment is usually given over five days. After this you can go home, depending on how you are feeling. 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.
Hyper-CVAD is usually given through a thin plastic tube that is either inserted under the skin and into a vein near the collarbone (central line) or passed through a vein in the crook of your arm (PICC line). Your doctor or nurse will explain more about this.
You will be given anti-sickness (anti-emetic) drugs by injection through your central line or PICC line. The steroid and chemotherapy drugs are given separately:
Cyclophosphamide (a colourless fluid) is given as a drip (infusion) over two hours.
Vincristine (a colourless fluid) and doxorubicin (a red fluid) are given as infusions.
Dexamethasone (a steroid) is given by mouth as tablets, or by injection through your central line or PICC line.
Methotrexate (a yellow fluid) is given as an infusion over 24 hours.
Cytarabine (a colourless fluid) is given as an infusion that lasts two hours.
In some situations, methotrexate and cytarabine may also be given by injection into the fluid around the spinal cord (intrathecal injection).
You will also be given lots of fluids (as an infusion) and a drug called mesna (Uromitexan®) with your cyclophosphamide to help prevent bladder irritation. You will also be given sodium bicarbonate - usually as an infusion - before and during your methotrexate treatment to help protect your kidneys. Another drug called folinic acid (sometimes called leucovorin) is given, usually into the vein or as tablets, to reduce the side effects of methotrexate.
How often treatment is given
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Your doctor may use the word 'regimen' (eg the Hyper-CVAD regimen) when talking about your chemotherapy. This means the whole plan, or schedule, of your particular chemotherapy treatment.
Chemotherapy is usually given as several sessions (cycles) of treatment. Usually up to eight cycles of Hyper-CVAD are given every 21 days. This means you will have four cycles of schedule A alternating with schedule B (see below).
If you are having Hyper-CVAD before a stem cell transplant, you will usually only have four sessions of chemotherapy (two of schedule A and two of schedule B).
Schedule A (cycles 1, 3, 5 and 7)
On the first day of your treatment, you will have cyclophosphamide, which is given twice in 24 hours. This will be repeated for the next two days (day 2 and 3).
You will also start taking dexamethasone tablets on the first day of treatment and continue taking these for four days.
On the fourth day of your treatment you will be given vincristine and doxorubicin. Doxorubicin is repeated again on the next day (day 5). You can usually go home the following day if you are well enough.
On day 11 of your treatment, you will have vincristine again (you can have this as a day patient) and you will start taking dexamethasone tablets for another four days. After this you will have a rest period, with no treatment for the next week. This completes a cycle of your treatment.
After the rest period you will then go on to have methotrexate and cytarabine (schedule B).
Schedule B (cycles 2, 4, 6, 8)
On the first day of treatment you will be given methotrexate continuously for 24 hours, and this is repeated on the next day. Cytarabine is given twice (12 hourly) on the second day and also on the third day. You can usually go home if you are well enough and your methotrexate levels are satisfactory. This is checked with a blood test.
After this you will have a rest period with no treatment for the next 18 days. This completes a cycle of your chemotherapy.
After the rest period you will then have Hyper-CVAD (schedule A). You will continue to alternate between schedule A and B until your chemotherapy treatment is completed.
When you go home after schedule A or B, you will be given a supply of anti-sickness tablets to take with you. It is important to take these as directed, even if you aren't feeling sick. This is because some anti-sickness drugs are much better at preventing sickness than stopping it once it begins.
Your central or PICC line will usually stay in place, ready for the next cycle of your chemotherapy. You will be shown how to look after the line.
You may need to have your blood checked every week between chemotherapy treatments or cycles. Some people may need to be admitted to hospital if they develop an infection or if the number of blood cells (blood count) is low. A blood transfusion or platelet transfusion to improve your blood count can be given to you during a short stay in hospital or as a day patient.
Each person’s reaction to chemotherapy is different. The side effects described here won't affect everyone who has Hyper-CVAD.
We have outlined the most common side effects but haven't included those that are rare and therefore unlikely to affect you. If you notice any effects that aren't listed here, discuss them with your doctor, chemotherapy nurse or pharmacist.
Risk of infection
Hyper-CVAD can reduce the number of white blood cells, which help fight infection. White blood cells are produced by the bone marrow. If the number of your white blood cells is low you will be more prone to infections.
A low white blood cell count is called neutropenia. This begins seven days after treatment, and your resistance to infection is usually at its lowest 10-14 days after chemotherapy. The number of your white blood cells will then increase steadily and usually return to normal before your next cycle of chemotherapy is due.
You may be given antibiotics to help prevent infections (known as prophylactic antibiotics).
Contact your doctor or the hospital straight away if:
your temperature goes above 38ºC (100.4ºF )
you suddenly feel unwell, even if you have a normal temperature.
You'll have a blood test before having more chemotherapy to check the number of white blood cells. Occasionally, your treatment may need to be delayed if your number of blood cells (blood count) is still low.
You may be given injections of G-CSF to help prevent the number of white blood cells getting too low. G-CSF is a type of protein that can stimulate the bone marrow to produce white blood cells. G-CSF is given as an injection under the skin (subcutaneously).
Bruising and bleeding
Hyper-CVAD can reduce the production of platelets, which help the blood to clot. Tell your doctor if you have any unexplained bruising or bleeding, such as nosebleeds, bleeding gums, blood spots or rashes on the skin. You can have a platelet transfusion if your platelet count is low.
Hyper-CVAD can reduce the number of red blood cells, which carry oxygen around the body. A low red blood cell count is called anaemia. This may make you feel tired and breathless. Tell your doctor or nurse if you have these symptoms. You may need to have a blood transfusion if the number of red blood cells becomes too low.
Feeling sick (nausea) or being sick (vomiting)
Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce, nausea or vomiting. If the sickness isn't controlled, or if it continues, tell your doctor; they can prescribe other anti-sickness drugs that may be more effective.
Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.
Feeling tired is a common side effect of chemotherapy, especially towards the end of treatment and for some weeks after it’s over. It’s important to try to pace yourself and get as much rest as you need. Try to balance this with taking some gentle exercise, such as short walks, which will help. If tiredness is making you feel sleepy, don’t drive or operate machinery.
Hair loss usually starts 3-4 weeks after starting treatment, although it may occur earlier. Hair usually falls out completely. You may also have thinning and loss of eyelashes, eyebrows and other body hair. This is temporary and your hair will start to grow again once the treatment has finished. Your hair may grow back straighter, curlier, finer or a slightly different colour than it was before. Your nurse can give you advice about coping with hair loss.
Your mouth may become sore or dry, 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 reduce the risk of this happening. Some people find sucking on ice soothing. Tell your nurse or doctor if you have any of these problems, as they can prescribe mouthwashes and medicine to prevent or clear mouth infections. You may find our section on mouth care during chemotherapy helpful.
You may notice that food tastes different. Normal taste usually comes back after treatment finishes. A dietitian or specialist nurse at your hospital can give you advice about ways of coping with this side effect.
Hyper-CVAD can cause diarrhoea. This can usually be easily controlled with medicine, but tell your doctor if it is severe or continues. It's important to drink plenty of fluids if you have diarrhoea.
Abdominal pain and constipation
Hyper-CVAD can cause pain in your tummy (abdomen) and constipation. Let your doctor know if you develop pain. It can usually be controlled with mild painkillers.
Constipation can usually be helped by drinking plenty of fluids, eating more fibre and doing gentle exercise. You may need to take medicine (laxative) to help. Your doctor can prescribe these or you can buy them at a pharmacy.
Irritation of the stomach lining
Dexamethasone can irritate the lining of the stomach and may cause a stomach ulcer or make one worse. You should take the tablets with a meal or a drink of milk to reduce this side effect. Tell your doctor if you have indigestion, or pain or discomfort in the tummy (abdomen). You may be prescribed medication to reduce irritation of the stomach.
Raised blood sugar
Occasionally dexamethasone can cause your blood sugar level to rise. During treatment you’ll have regular blood tests to check this. Your urine may also be tested for sugar.
Tell your doctors if you get very thirsty or if you’re passing more urine than usual. This can be a sign that your blood sugar level is rising.
Appetite changes and weight gain
You may notice that you feel hungrier than usual while taking dexamethasone, and this can make you want to eat more. If you’re concerned about gaining weight, you can speak to your doctor, specialist nurse or dietitian. You might find our section on weight management useful.
Behavioural changes and mood swings
Occasionally steroids can cause mood swings, difficulty sleeping and anxiety or irritability. Let your doctor know if there are any changes in your behaviour that are worrying you. Difficulty with sleeping may be helped by taking the steroids in the early part of the day, but discuss this with your doctor first.
Numbness or tingling in the hands or feet
This is due to the effect of vincrisitne on nerves and is known as peripheral neuropathy. You may also notice that you have difficulty doing up buttons or similar fiddly tasks. Tell your doctor if you notice any numbness or tingling in your hands or feet. It is important to report your symptoms to your doctor as they may be controlled by slightly lowering the dose of the drug. This side effect usually improves slowly, a few months after the treatment has finished. Sometimes symptoms can persist. Talk to your doctor if this happens.
Raised levels of uric acid in the blood
This can result in a condition called gout, which causes inflammation of the joints. To prevent this, you may be given a drug called allopurinol (Zyloric®) and you may be asked to drink plenty of fluids. While you are having Hper-CVAD you may have regular blood tests to check your uric acid levels.
A skin rash can sometimes occur while you're having treatment with Hyper-CVAD. It’s important to let your doctor know if this happens. Your doctor can prescribe medicine to help with this. Cytarabine can cause soreness and redness of the palms of the hands and soles of the feet. This is temporary and usually improves once treatment finishes.
Rarely, your skin may darken. If it does, it usually goes back to normal a few months after the treatment has finished. During treatment and for several months afterwards, you will be more sensitive to the sun and your skin may burn more easily than normal. You can still go out in the sun, but should wear a suncream with a high sun protection factor (SPF) and cover up with clothing and a hat. Sometimes areas of skin that have been treated with radiotherapy may become red and sore. Tell your doctor if this happens.
You might find our page on taking care in the sun useful.
Hyper-CVAD may cause an inflammation of the lining of the eyelids (conjunctiva) that makes your eyes feel sore, red and itchy. Let your doctor know so they can prescribe soothing eye drops if necessary.
You may develop flu-like symptoms a few hours after cytarabine has been given. These include headaches, aching joints or muscles, a temperature, lack of energy (lethargy) and chills. If this happens, it's important to drink plenty of fluids and get some rest. If these symptoms continue for more than a day contact your doctor.
Your urine may become a pink-red colour. This may last up to 48 hours after you’ve had your treatment. It is normal and is due to the colour of the doxorubicin.
Cyclophosphamide may irritate your bladder. It’s important to drink as much fluid as you can (at least two litres) during the 24 hours following chemotherapy to help prevent this. Let your doctor know if you have any discomfort when you pass urine, or if you notice any blood in it. You will also be given fluids through a drip (infusion), along with a drug called mesna (Uromitexan®), to help prevent bladder irritation.
Changes to the lungs
Chemotherapy may cause some changes to the lungs. Tell your doctor if you smoke or if you notice any coughing or breathlessness.
Effects on the nervous system
Standard doses of cytarabine rarely have any effect on the nervous system. But high-dose treatment with cytarabine can cause temporary or occasionally permanent changes to the nervous system. This may cause a variety of symptoms, including seizures (fits), drowsiness, unsteadiness and mood changes. Tell your doctor straight away if you have any of these symptoms.
Effect on the kidneys
Very high doses of methotrexate can damage the kidneys, but it’s rare for this to happen when standard doses are given. To prevent this you may be given sodium bicarbonate, either as an infusion into the vein or as tablets or capsules, before and during the methotrexate treatment. You will have a blood test before each methotrexate treatment to check your kidneys are working normally.
Treatment with Hyper-CVAD may cause changes in the way that your liver works, although it will return to normal when the treatment finishes. You're very unlikely to notice any problems, but your doctor will take regular blood samples to check your liver is working properly.
Changes in the way your heart works
This is very rare with standard doses of doxorubicin, but it may occasionally occur with high-dose treatment. The muscle of the heart may be affected, usually temporarily. Tests to see how well your heart is working may be carried out before the drug is given and sometimes before each treatment.
Always let your doctor or nurse know about any side effects you have. There are usually ways in which they can be controlled or improved.
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Risk of developing a blood clot
Cancer can increase the risk of developing a blood clot (thrombosis), and 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’s important to tell your doctor straight away if you notice any of these symptoms. Most clots can be treated with drugs that thin the blood. The doctor or nurse can give you more information.
Some medicines, including those that you can buy in a shop or chemist, can be harmful to take when you are having chemotherapy. Tell your doctor about any medicines you are taking, including over-the-counter drugs, complementary therapies and herbal drugs.
Folinic acid rescue
A drug called folinic acid (sometimes called leucovorin) is usually given 24 hours after starting methotrexate treatment to reduce side effects. When it's given after methotrexate treatment, it's often called ‘folinic acid rescue'. While you are attached to a drip, the folinic acid can be given into the vein (intravenously). Otherwise it is given as tablets. It’s very important to take the folinic acid on time and to take all the tablets as directed by your doctor.
Leakage into the tissue around the vein (extravasation)
If this happens when doxorubicin or vincristine is being given, the tissue in that area can be damaged. Tell the doctor or nurse immediately if you notice any stinging or burning around the vein while the drug is being given. This is unlikely to happen if the chemotherapy is given through a central line or PICC line.
If the area around the injection site becomes red or swollen at any time, you should tell the doctor or nurse on the ward. If you are at home, ring the clinic or ward and ask to speak to the doctor or nurse.
Your ability to become pregnant or father a child may be affected by having this treatment. It's important to discuss fertility with your doctor before starting treatment.
It's not advisable to become pregnant or father a child while having Hyper-CVAD, as it may harm the developing baby. It’s important to use effective contraception while taking this drug and for at least a few months afterwards. You can discuss this with your doctor.
It’s not known whether chemotherapy drugs can be present in semen or vaginal fluids. To protect your partner, it’s safest to either avoid sex or use a barrier form of contraception for about 48 hours after chemotherapy.
There is a potential risk that chemotherapy drugs may be present in breast milk, so women are advised not to breastfeed during chemotherapy and for a few months afterwards.
Loss of periods in women
Because of the effect of chemotherapy on the ovaries, women may find that their periods become irregular and may eventually stop. In some women this may be temporary, but for others it will be permanent. This will result in menopausal symptoms such as hot flushes, sweats and vaginal dryness.
If you’re admitted to hospital for a reason not related to the cancer, it’s important to tell the doctors and nurses looking after you that you are having chemotherapy treatment. You should tell them the name of your cancer specialist so that they can ask for advice.
It’s a good idea to know who you should contact if you have any problems or troublesome side effects when you’re at home. Your chemotherapy nurse or doctor will give you details of who to contact for advice. This should include ‘out-of hours’ contact details if you need to call someone at evenings, overnight or at the weekend.
This section is based on our Hyper-CVAD fact sheet, which has been compiled using information from a number of reliable sources, including:
Sweetman, et al. Martindale: The Complete Drug Reference. 37th edition. 2011. Pharmaceutical Press.
British National Formulary. 62nd edition. 2011. British Medical Association and Royal Pharmaceutical Society of Great Britain.
Perry MC. The Chemotherapy Source Book. 4th edition. 2007. Lippincott Williams and Wilkins.