Angiogenesis inhibitors

Thalidomide

This section is about thalidomide – a drug that was developed to prevent morning sickness in pregnant women. Research is now looking at if it is effective in treating some types of cancer. This section aims to give a balanced summary of the information available so far.

  • Understanding cancer research trials
  • About Thalidomide
  • How does it work?
  • What it looks like
  • How is it given
  • Possible side effects
  • Additional information
  • References

Understanding cancer research trials

When a drug is being developed it has to go through various stages of research, called clinical trials or studies. These are intended to establish a safe dosage and find out what side effects the drug may cause. Trials can also show how effective a drug is, and whether it is better than the existing treatments, or provides extra benefit when given alongside existing treatment.

Currently thalidomide is available only to a small number of people in the UK, usually those taking part in the research trials. In certain circumstances it may also be given to particular patients if their specialist thinks it may help (this is called prescribing on a named patient basis).

Many drugs thought at first to be promising, may be found to be less effective than existing treatments, or to have side effects that outweigh any benefits. For this reason, doctors and other medical staff carry out frequent and careful checks on the progress of each patient being treated with a drug such as thalidomide.

If you are prescribed thalidomide, your doctor will explain all about the drug, the procedures being used, and how you will be looked after while you are taking it. If at any time you have concerns, you should ask your doctor or nurse for information and advice.

About Thalidomide

Many people have heard of thalidomide. Its use in treating sickness during pregnancy in the 1960s resulted in birth defects. The birth defects were caused because thalidomide changes the growth and development of new blood vessels. It affected the formation of blood vessels in the developing babies.

Generally, thalidomide is only available in specialist cancer treatment centres and where research trials are taking place and specialist doctors have experience in its use. It is most commonly used to treat a type of cancer known as myeloma.

How does it work?

Cancers need to produce a network of new blood vessels to continue to grow. Without forming these new blood vessels, cancers cannot grow larger than a pinhead. Researchers are hoping to use thalidomide to stop cancers from developing new blood vessels. This should reduce the cancer’s supply of oxygen and nutrients, which, it is hoped, will cause the tumour to shrink, or at least to stop growing. Drugs that interfere with blood vessel growth in this way are called angiogenesis inhibitors or anti-angiogenics.

Thalidomide can also be helpful in reducing some of the unpleasant symptoms that people with cancer may have. A substance produced naturally in the body, called tumour necrosis factor (TNF), stimulates the immune system to attack any cells that may be harmful. When people have cancer, they may produce too much TNF. This causes their immune system to overreact and can lead to high temperatures, night sweats and severe weight loss. Thalidomide reduces the amount of TNF produced in the body and therefore may be used to control these symptoms.

What it looks like

Thalidomide is available as white 25mg, 50mg or 100mg capsules.

How is it given

Thalidomide tablets or capsules are swallowed whole with plenty of water an hour after food, preferably in the late evening. It may be given in combination with chemotherapy drugs.

Possible side effects

Birth defects  You must not become pregnant or father a child while taking thalidomide as it causes severe abnormalities in developing babies. Women will be asked to have a pregnancy test to check that they are not pregnant. They will also be advised to use a highly effective form of contraception (such as implanted, or injected contraception) as well as a barrier method (such as a condom or cap). Men taking thalidomide are advised to use a condom during sexual intercourse even if they have had a vasectomy.

Nausea (feeling sick) and vomiting  Most people have little or no nausea. You will probably be given anti-sickness medication to take, but tell your doctor if the nausea becomes a problem.

Temporary reduction in the production of blood cells by the bone marrow, which can result in anaemia, risk of bruising or bleeding and infection  Thalidomide has only a slight effect on bone marrow. However, it is usually given in combination with chemotherapy drugs. The extent to which your bone marrow is affected depends on which chemotherapy drugs, if any, are given in combination with the thalidomide. Your blood will be checked regularly to see how well your bone marrow is working. If your temperature goes above 38°C (100.5°F), or you develop any unexplained bruising or bleeding, or you suddenly feel unwell, even if you have a normal temperature, contact your doctor or the hospital straight away.

Lethargy, sleepiness and loss of balance  It is not unusual for people to feel sleepy when taking thalidomide. It is important to tell your doctor if you have these side effects. However, they may improve as you continue to take the drug. If you are sleepy, it is important not to drive or operate machinery.

Constipation  This can usually be relieved by drinking plenty of fluids (2–3 litres per day), eating a high-fibre diet and taking gentle exercise. Sometimes you may need to take medicines to stimulate your bowel. These can be prescribed by your doctor.

Loss of appetite A dietitian or specialist nurse at your hospital can give advice.

Numbness or tingling in hands or feet  This effect is uncommon if you have standard doses of the drug, but it may happen if you have very high-dose treatment. This is due to the effect of thalidomide on the nerves and is known as peripheral neuropathy. You may also notice that you have difficulty in tasks like doing up buttons. Tell your doctor if you notice any of these side effects. They usually improve slowly a few months after the treatment ends.

Headache  Let your doctor know if you have headaches while having treatment with thalidomide.

Dizziness on standing You may feel dizzy for a few moments if you stand up too suddenly. This is caused by a temporary fall in blood pressure. Move slowly from lying to sitting and then sitting to standing. Tell your doctor if you have ever had any blood pressure problems, and about any medicines you are taking.

Rashes Thalidomide can cause a rash, which may be itchy. Your doctor can prescribe treatment to help reduce this.

Swelling and fluid retention  You may find that you develop swollen ankles, particularly if you have been standing still or sitting down for a time. Try to remember to keep your feet up if you are sitting still. Talk to your doctor about medicines that may help. If the swelling is uncomfortable, your doctor may be able to prescribe elastic stockings to keep it under control.

If you have any questions about these or any other side effects do talk to your doctor or nurse. It is important to let them know if you have any symptoms or side effects that may be related to any treatment you are having.

Additional information

  • It is important to take your capsules at the right times. You must take them as directed by your doctor.
  • Keep the capsules in a safe place where children cannot reach them, as thalidomide could harm them.
  • If your doctor decides to stop the treatment, return any remaining capsules to the pharmacist. Do not flush them down the toilet or throw them away.
  • If you forget to take a capsule do not take a double dose. Tell your doctor and keep to your regular dose schedule.
  • If you are sick just after taking the tablet tell your doctor as you may need to take another one.
  • Thalidomide may interact with alcohol. It is advisable not to drink alcohol while taking thalidomide.
  • Thalidomide may interact with other medicines that you are taking. Let your doctor know what medications you are taking.

References

This section has been compiled using information from a number of reliable sources including:

  • Oxford Textbook of Oncology (2nd edition). Souhami et al. Oxford University Press, 2002.
  • Martindale: The Complete Drug Reference (33rd edition). Sweetman et al. Pharmaceutical Press, 2002.

For further references, please see the general bibliography.

Bevacizumab (Avastin™ )

This section is about bevacizumab, a new drug that is being used to treat some types of cancer. This section aims to give a balanced summary of the information available so far. Bevacizumab is also called Avastin™.

  • About bevacizumab
  • How does it work?
  • What it looks like
  • How it is given
  • Possible side effects
  • References

About bevacizumab

When a drug is being developed it has to go through various stages of research, called clinical trials or studies. These are intended to establish a safe dose and find out what side effects the drug may cause. Trials can also show how effective a drug is, and whether it is better than the existing treatments, or has extra benefit when given alongside existing treatment.

Research trials have been carried out giving bevacizumab with chemotherapy to people with cancer of the bowel (colon or rectum) that has spread to other parts of the body. People given chemotherapy and avastin lived slightly longer than people who were given chemotherapy alone. Bevacizumab cannot cure cancer of the bowel that has spread, but it can help to control the cancer for a time.

Bevacizumab is being used in the USA alongside chemotherapy for advanced colon cancer. It is also being used in early trials to treat some other types of cancer such as breast, lung and kidney cancer.

Currently bevacizumab is not licensed in the UK and is only available to a small number of people, usually those who are taking part in research trials. In some circumstances it may also be given to particular patients if their specialist thinks it may help (this is called prescribing on a named patient basis).

As bevacizumab is a new drug, medical and nursing staff carry out frequent and careful checks on the progress of each patient being treated with it.

If you are prescribed bevacizumab, your doctor will explain all about the drug, the procedures being used, and how you will be looked after while you are taking it. If at any time you have concerns, you should ask your doctor or nurse for information and advice.

How does it work?

Cancers need to produce a network of new blood vessels to continue to grow. Without forming these new blood vessels, cancers cannot grow larger than a pinhead. Bevacizumab can stop some cancers from developing new blood vessels. This reduces the cancer’s supply of oxygen and nutrients, which causes the tumour to shrink, or at least to stop growing. Drugs that interfere with blood vessel growth in this way are called angiogenesis inhibitors or anti-angiogenics.

What it looks like

Bevacizumab is produced as a liquid. The nurse or pharmacist will prepare the drug.

How it is given

Bevacizumab liquid is given into a vein, through a small tube (cannula) inserted into the vein. It may be given in combination with chemotherapy drugs, usually irinotecan, fluorouracil and leucovorin.

Some people have their bevacizumab and chemotherapy given through a fine plastic tube which is inserted under the skin into a vein near the collarbone (central line) or passed through a vein in their arm (PICC line). Your doctor or nurse will explain more about this to you.

Possible side effects

Each person’s reaction to cancer treatment is unique. Some people have very few side effects, while others may experience more. The side effects described in this section will not affect everyone who is given bevacizumab. The drug is often used in combination with chemotherapy, so patients will also have side effects from the chemotherapy. The side effects mentioned below are those caused by bevacizumab.

We have outlined the most common side effects, but have not included those that are very rare and therefore extremely unlikely to affect you. If you notice any effects which you think may be due to the drug, but which are not listed here, please discuss them with your doctor or nurse.

High blood pressure  If you have any headaches, nosebleeds or feelings of dizziness let your doctor know. Your blood pressure will be checked regularly.

Slow wound healing  Wounds may take longer to heal while you are having treatment with bevacizumab

Tiredness and a general feeling of weakness  It is important to allow yourself plenty of time to rest. CancerBACUP has a section on coping with tiredness.

Bruising or bleeding  Bevacizumab can reduce the production of platelets, which help the blood to clot. Let your doctor know if you have any unexplained bruising or bleeding.

Diarrhoea This can usually be easily controlled with medicine but let your doctor know if it is severe or continues. It is important to drink plenty of fluids if you get diarrhoea.

Headaches  Let your doctor know if you have headaches whilst you are having bevacizumab treatment.

Nausea and vomiting  There are very effective anti-sickness drugs to prevent or greatly reduce nausea and vomiting. If it happens it may begin a few hours after the treatment is given and last for up to a few days. If the sickness is not controlled, or continues, tell your doctor, who can prescribe other anti-sickness drugs which may be more effective. CancerBACUP has a section on managing nausea and vomiting.

Sore mouth and taste change  Your mouth may become sore, 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 doctor if you have any of these problems as they can prescribe special mouthwashes and medicine to prevent or clear any mouth infection.

Loss of appetite You may find that you do not feel like eating. CancerBACUP’s section on diet and the cancer patient has helpful tips on boosting appetite and a dietitian at the hospital can give advice.

Damage to the kidneys  Bevacizumab can sometimes temporarily change the way that your kidneys work. You may have blood tests to check that your kidneys are working well.

Pain in the area of the tumour  Some people may have pain in the area of the tumour.

If you have any questions about these or any other side effects, talk to your doctor or nurse. It is important to let them know if you have any symptoms or side effects that may be related to any treatment you are having.

References

This section has been compiled using information from a number of reliable sources including:

  • Website of the Federal Drug Adminuitration – www.fda.gov
  • Website of the National Cancer Instritite, USA – www.cancer.gov
  • Website of Genentech and Roche– www.Roche.com
Angiogenesis inhibitors

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