This information is about a chemotherapy treatment called Hyper-CVAD, which can be used to treat some types of non-Hodgkin lymphomas (cancers of the lymphatic system) and acute lymphoblastic leukaemia (ALL). It describes the drugs used, how they are given and some of their possible side effects. If you have any further questions you can ask your doctor or nurse at the hospital where you are having your treatment, or speak to one of our cancer support service nurses.

Hyper-CVAD is named after the initials of the chemotherapy drugs used. These are cyclophosphamide, vincristine, doxorubicin (also known as Adriamycin®) and dexamethasone, which is a steroid.

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, which 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 for short.

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.

You will need to have a blood test before you start treatment – 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 inserted under the skin into a vein near the collar bone (central line) or passed through a vein in your arm (PICC line). Your doctor or nurse will explain more about this to you.

You will be given anti-sickness (antiemetic) 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 over two hours
• vincristine (a colourless fluid) and doxorubicin (a red fluid) are given as a drip
• dexamethasone (a steroid) is given by mouth or by injection through your central line or PICC line
• methotrexate (a yellow fluid) is given as a drip over 24 hours
• cytarabine (a colourless fluid) is given as a drip over 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 a drip) and a drug called mesna with your cyclophosphamide to help prevent bladder irritation. Sodium bicarbonate will be given to you – usually as a drip – 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.

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 the particular chemotherapy treatment that you are having.

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 (methotrexate and cytarabine).

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 on 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 doxorubicin and vincristine. 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. After this you will have a rest period with no treatment for the next 18 days. This completes a cycle of your chemotherapy.

After schedule B, you can usually go home once your methotrexate levels are satisfactory (this is checked with a blood test) and you are well enough.

After the rest period you will then go on to have Hyper-CVAD (schedule A). You will continue to alternate between schedule A and B until your chemotherapy treatment is completed.

Going home

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 are not feeling sick. This is because some anti-sickness drugs are much better at preventing sickness than at stopping it once it has started. You may also be given some antibiotics to take as a preventative measure.

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 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. Some people have very few side effects, while others may experience more. The side effects described here will not affect everyone who is having Hyper-CVAD.

We have outlined the most common side effects, so that you can be aware of them if they occur. However, we have not included those that are rare and therefore unlikely to affect you. If you notice any effects that you think may be due to the drugs, but that are not listed here, please let your nurse or doctor know.

Lowered resistance to infection Hyper-CVAD reduces the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin about seven days after treatment has been given, with your resistance to infection usually reaching its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily and will usually have returned to normal levels before your next cycle of chemotherapy is due. You may be given antibiotics to take as a preventative measure (known as prophylactic antibiotics).

You will need to have antibiotics if you develop a temperature. Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.5ºF )
• you suddenly feel unwell (even if you have a normal temperature).

You will have a blood test before having more chemotherapy to make sure that your number of white blood cells has returned to normal. Occasionally, it may be necessary to delay treatment if your number of blood cells (blood count) is still low.

You may be given injections of a drug called G-CSF (granulocyte-colony stimulating factor), which is a protein that can help to boost the number of white blood cells that your bone marrow produces. It is given as an injection under the skin (subcutaneously).

Bruising or bleeding Hyper-CVAD can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, or bleeding gums. You can have a platelet transfusion if your platelet count is low.

Anaemia (low number of red blood cells) You may become anaemic while having this treatment. This can make you feel tired and breathless. Let your doctor or nurse know if these effects are a problem. Blood transfusions are often given to correct anaemia.

Feeling sick (nausea) and being sick (vomiting) Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent or reduce nausea and vomiting. If the sickness is not controlled, or if it continues, tell your doctor. They can prescribe other anti-sickness drugs which may be more effective. Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.

Tiredness Many people feel extremely tired during chemotherapy, particularly towards the end of treatment. This is a common side effect and it is important to try to get as much rest as you need.

Hair loss This usually starts 3–4 weeks after the first course of treatment. All your hair will usually fall out. You may also have thinning and loss of eyebrows and other body hair. The hair loss is temporary and your hair will start to grow back once the treatment has finished.

Sore mouth and ulcers 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 to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as they can give you special mouthwashes and medicine to prevent or clear any mouth infection.

Taste changes You may notice that your food tastes different. Normal taste will usually come back after treatment finishes.

Diarrhoea This can usually be easily controlled with medicine but tell your doctor if it is severe or persistent. It is important to drink plenty of fluids if you have diarrhoea.

Abdominal cramps and constipation It usually helps to drink plenty of fluids, eat a high-fibre diet and take gentle exercise. Sometimes you may need to take medicines to stimulate your bowel. These can be prescribed by your doctor.

Irritation of the stomach lining Dexamethasone (a steroid) may irritate the lining of your stomach and should be taken with meals or a glass of milk. Tell your doctor if you have indigestion or any other stomach problems. They can prescribe medicine to relieve these symptoms.

Changes in the level of sugar in your blood Dexamethasone may cause your blood-sugar to rise. During treatment you will have blood and urine tests to check this.

Increased appetite You may notice that you feel hungrier than usual while taking dexamethasone. This will stop are no longer taking the drug.

Changes in behaviour You may experience mood swings, difficulty sleeping, and perhaps anxiety or irritability. These effects can happen because of the steroids you are taking. Tell your doctor about any changes 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 hands or feet This is due to the effect of vincristine on nerves and is known as peripheral neuropathy. Tell your doctor if you notice any numbness or tingling in your hands or feet. This usually improves slowly a few months after treatment is finished.

Raised levels of uric acid in the blood These can occur when a person has cytarabine. A drug called allopurinol may be given to stop this happening. It may also help to drink plenty of fluids. While you are taking cytarabine, your uric acid levels may be checked by blood tests.

Skin changes Rarely your skin may darken. If it does, it usually goes back to normal a few months after the treatment is finished. Some of the drugs can cause a rash that may be itchy and your doctor can prescribe medicine to help with this.

During treatment, and for several months afterwards, you will be more sensitive to the sun and your skin may burn more easily. You can still go out in the sun but always wear a high protection-factor sun cream and cover up with clothes. Sometimes areas that have previously been treated with radiotherapy may become red and sore. Let your doctor know if this happens.

Soreness and redness of the palms of the hands and soles of the feet This is sometimes known as palmar plantar or hand and foot syndrome. It is temporary and will improve when the treatment is finished.

Gritty and sore eyes This can be caused by inflammation of the cornea or of the lining of the eyelids (conjunctiva). If this happens, it is important that you tell your doctor. You may be given steroid eye drops to soothe your eyes and prevent conjunctivitis.

Flu-like symptoms This can occur after cytarabine is given, and may last for a few days. You may have headaches, aching joints or muscles, a temperature, lethargy (a feeling of having no energy) and chills.

Irritation of the bladder Cyclophosphamide may irritate your bladder. It is important to try to drink plenty of fluids to prevent any irritation. You will be given fluids into your vein before and after the chemotherapy is given. You will also be given a drug called mesna to protect the bladder and kidneys.

Doxorubicin is a shade of red, and your urine may become a pink-red colour as a result. This may last up to 24 hours after your treatment and is quite normal.

Changes to the lungs Tell your doctor if you notice any coughing or breathlessness.

Effect on the nervous system Cytarabine in very high doses can cause some damage to the nerves inside and outside the brain. This may cause a variety of symptoms, including seizures (fits) and mood changes.

Your kidneys may be affected Methotrexate in very high doses can damage the kidneys. To prevent this happening you may be given sodium bicarbonate, usually as an infusion into the vein, before and during the methotrexate treatment. You will have a blood test before each methotrexate treatment to check your kidneys are working normally.

Your liver may be temporarily affected Some of the drugs may cause changes in the way that your liver works, though it will return to normal when the treatment is finished. This is unlikely to cause you any harm but your doctor will monitor this carefully. Samples of your blood will be taken regularly to check your liver is working properly.

Changes in the way your heart works This is very rare with standard doses of doxorubicin but may occasionally happen when high doses are used. Tests to see how well your heart is working may be carried out before you start your treatment.

Risk of blood clots Cancer can increase your risk of developing a blood clot (thrombosis), and having 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 is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated by using drugs which thin the blood. Your doctor or nurse can give you more information. 

Other medicines Some other medicines can be harmful to take when you are having chemotherapy. Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

A drug called folinic acid (sometimes called leucovorin) is usually given 24 hours after starting methotrexate treatment, to reduce the side effects. 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 that you take the folinic acid on time and that you take all the tablets as directed by your doctor. It is often called ‘folinic acid rescue' when it is given in this way after methotrexate treatment.

Leakage into the tissue around the vein (extravasation) If this happens when doxorubicin or vincristine are being given, the tissue in that area can be damaged. If you notice any stinging or burning around the vein while the drug is being given, tell the doctor or nurse immediately. This is unlikely to happen if the chemotherapy is given through a central or PICC line.

Fertility Your ability to become pregnant or father a child may be affected by having this treatment. It is important to discuss fertility with your doctor before starting treatment.

Loss of periods in women Due to the effect of chemotherapy on the ovaries you may find that your periods become irregular and may eventually stop. In younger women this may be temporary but if you are closer to your menopause it may be permanent. This will result in menopausal symptoms such as hot flushes, sweats and vaginal dryness.

Contraception It is not advisable to become pregnant or father a child while taking this treatment, as it may harm the developing foetus. It is important to use effective contraception while taking this drug, and for some time afterwards. Again, discuss this with your doctor.

This section is based upon our Hyper-CVAD chemotherapy factsheet which has been compiled using information from a number of reliable sources, including:

• Martindale: The Complete Drug Reference (35th edition), Eds. Sweetman et al, Pharmaceutical Press, 2007.
• British National Formulary (54th edition), British Medical Association and Royal Pharmaceutical Society of Great Britain, September 2007.
• The Chemotherapy Source Book (3rd edition), Ed. Perry, Lippincott, Williams and Wilkins, 2001
• Kantarjan HM , et al. Results of treatment with Hyper-CVAD, a dose intensive regimen, in adult acute lymphocytic leukaemia. Journal Clinical Oncology, 2004, 18 (3);547-61.

For further references, please see the general bibliography.