Iodine 131 tositumomab (BEXXAR)

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, the side effects the drug may cause and which cancers it may be used to treat. The trials also find out how effective the drug is, and whether it is better than the existing treatments or has extra benefit when given with these drugs.

At this stage BEXXAR is available only to a small number of people in the UK, usually those taking part in clinical trials. In certain circumstances it may also be given to individual patients who have been selected by their doctor as suitable (this is called a named patient basis).

Many drugs that are thought to be promising may be found not to be as good as 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 who is having one of these developmental drugs. If you are taking a developmental drug 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.

BEXXAR

BEXXAR is a new type of cancer treatment that involves a group of drugs called monoclonal antibodies. At the moment it is used only in clinical trials to treat a type of B-cell non-Hodgkin’s lymphoma (NHL) that has come back after previous treatment.

What is a monoclonal antibody?

Monoclonal antibodies recognise certain proteins that are found on the surface of some cancer cells. They are used to try to destroy the cancer cells, while causing little harm to normal cells. The monoclonal antibody recognises the protein on the surface of the cancer cell and locks on to it (like a key in a lock). Some monoclonal antibodies can then trigger the body’s immune system to attack the cancer cells and can also cause the cells to destroy themselves. Sometimes monoclonal antibodies, such as BEXXAR, have a cancer drug or radioactive substance attached to them. They can be used in this way to deliver treatment directly to the cancer cell: this is known as targeted therapy.

How does BEXXAR work?

BEXXAR has a radioactive substance called iodine131 attached to it. The monoclonal antibody in BEXXAR, tositumomab, targets a protein found on the surface of the B-cells. The radioactive iodine delivers radiation directly to these cells. This destroys the lymphoma B-cells. Unfortunately it may also affect some normal cells.

How is it given?

BEXXAR is given as a drip (infusion) into the vein, through a fine tube (cannula) inserted into the vein. It is usually given in the nuclear medicine department of your hospital. You will usually need to make four visits over one to two weeks. The first three visits are needed to decide how much radioactivity you will be given and the fourth will actually be the treatment.

Before you start treatment and for two weeks after you are given the treatment dose of BEXXAR, you will need to take a daily iodine supplement. This is taken either as tablets or as liquid drops and helps to protect the thyroid gland from the radioactive iodine.

On the first day of treatment you will be given two separate drips. Before these drips you will be given paracetamol and an antihistamine to help reduce any side effects that may occur. The first drip is an infusion of the monoclonal antibody without any radioactive iodine which is given to you over an hour. This is given to ensure that when you have the second infusion, which contains the radioactivity, it will be evenly spread throughout your body.

The second drip contains the monoclonal antibody with a small amount of radioactive iodine131. This small dose of radioactivity is given to see how the radiation is spread around the body and to help the doctors to decide exactly how much radioactive iodine to give you. Soon after this second infusion you will have the first of three body scans. This takes between 15–30 minutes and shows how much radioactivity is still in the body and where it is.

On the second visit (day 2, 3 or 4) you will have another body scan to see whether there is any radioactivity left in the body.

The third visit on day 6 or 7 involves another body scan. After this the doctors can calculate exactly how much radioactivity to add to the monoclonal antibody to ensure that you get the best possible dose.

The fourth visit (between days 7 and 14) is when you actually have the treatment dose of BEXXAR. You will receive two drips into your cannula, the first one of just the monoclonal antibody, over an hour, and the second containing the dose of radioactive antibody, given over 20 minutes.

After the fourth visit you will need to stay in hospital for a few days because of the possibility of unnecessary radiation exposure to other people. The risk to other people is small and lasts for up to a week until the radiation has been got rid of from your body through your sweat and urine. Certain restrictions will be needed during this time.

You will probably be looked after in a room of your own or with someone else having similar treatment. Lead screens will be placed at either side of your bed to absorb any radiation that is given out. Visiting times will be restricted and pregnant women and children will not be allowed to visit. However, you should feel well and can bring books and magazines into your room, watch TV or listen to the radio to help pass the time.

CancerBACUP’s general information on radiotherapy explains more about treatment with a radioactive substance.

Possible side effects

The known side effects of BEXXAR are not usually severe. However, as it is still a relatively new drug it is too early to know all about the possible side effects. The following appear to be the most common.

Flu-like symptoms These may include fever and chills, headaches, itching and joint and muscle aches. These effects may occur a few hours after the drug is given but do not usually last for more than a day or two.

Temporary reduction in production of blood cells by the bone marrow This can result in a lowering of the number of white cells (which fight infection) in your blood making you more prone to infection. It can also result in bruising or bleeding if your platelets (cells which clot the blood) are reduced, or anaemia if your red cells are low. Your doctor or nurse will advise you about this and any precautions you should take. The blood cells usually recover in three to four weeks.

Allergic reactions  The drug does not usually cause many problems. However, it is possible to have a slight allergic reaction to the monoclonal antibody in BEXXAR. Signs of this include skin rashes and itching, a feeling of swelling in the tongue or throat, irritation of the nasal passages, wheezing, a cough and breathlessness.

You will be monitored closely during your treatment, but tell the nurse or doctor if you have any of these symptoms. To reduce the chance of developing an allergic reaction certain drugs (anti-histamines) can be given before the drip. The drip can be slowed down or stopped until the reaction is over.

Other side effects include weakness and nausea (feeling sick). Your doctor can prescribe anti-sickness drugs to help reduce this.

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.
  • Treatment of Cancer (4th edition). Price and Sikora. Arnold, 2002.

For further references, please see the general bibliography.

Cetuximab (Erbitux©)*

What is Cetuximab

Cetuximab is a type of drug known as a monoclonal antibody. It is not currently licensed for use in the UK and is only available to a small number of people, usually those taking part in research trials. In certain circumstances it may be given to patients if their cancer specialist thinks that it may help them and the drug manufacturer agrees (this is called prescribing on a named patient basis).

Cetuximab is being used in the USA in early trials to treat many different types of cancer, including colon cancer, kidney (renal) and bladder cancers, cancer of the head and neck, breast cancers, pancreatic cancer, non-small cell lung cancer, and ovarian cancer. These studies are being carried out on cancers that have come back after initial treatment, or have spread to other parts of the body (advanced or metastatic cancer).

Cetuximab can be given as a treatment on its own or in combination with chemotherapy or radiotherapy.

What is a monoclonal antibody?

Monoclonal antibodies are used to try to destroy some types of cancer cells while causing little harm to normal cells. They are designed to recognise certain proteins (receptors) that are found on the surface of particular cancer cells. The monoclonal antibody recognises the protein and locks onto it. This may trigger the body’s immune system to attack the cancer cells and can sometimes make the cells destroy themselves.

On the surface of some cancer cells are receptors known as epidermal growth factor receptors or EGFR. When growth factors (such as transforming growth factor alpha and epidermal growth factor) bind to the receptor, the cancer cell is stimulated to grow, divide and spread. New blood vessels may grow to feed the cancer cells.

Cetuximab locks onto the EGFR, preventing the growth factors from stimulating the cancer cell to grow, divide and spread. It may do this by preventing the cancer cell from producing the network of new blood vessels that it needs to grow. It stops the cancer cells from growing and spreading to other parts of the body and can sometimes kill the cells.

Cetuximab may also make the cancer cells more sensitive to chemotherapy.

Tests may be done to find the level of EGFR in the body before cetuximab is given. This can help the doctors to know whether you are likely to benefit from this treatment. Testing can be done at the same time as diagnosis of the cancer, or samples of cancer cells from previous biopsies or surgery may be used.

What it looks like

Cetuximab is a colourless liquid.

How it is given

Cetuximab is given by a drip into the vein (intravenously) through a fine tube (cannula) inserted into a vein. The first dose is given slowly, usually over two hours. After this doses are given weekly and this normally takes about an hour. The first dose is usually larger than the weekly ‘maintenance’ treatments. You may be given other medicines before cetuximab to lessen the side effects during treatment.

Possible side effects

Each person’s reaction to a cancer drug is unique. Some people have very few side effects, while others may experience more. If you do notice any effects which you think may be due to the drug, but which are not listed here, please discuss these with your doctor.

The side effects of cetuximab are generally mild and some of these can be reduced with medicines. As it is still a new drug it is too early to know about all the possible side effects.

Skin changes Mild skin rashes are very common. They begin during the first two weeks of treatment and usually go away completely when the treatment stops. Some people have more severe skin changes, which can include reddening of the skin and red pimples and spots on the face. The skin of the face may also become flaky and scaly. Some people have dry skin eczema on their fingertips, elbows and extremities, which is sore and itchy. If you have any of these skin changes let your doctor know straight away. If you have very severe skin problems the length of time between the treatments may be extended or the dose may be lowered.

Treatment can be prescribed by your doctor to reduce the rash. To help reduce the reddening it is best to avoid foods that make the skin go red, such as chillies and alcohol.

To help reduce the dry skin eczema it is helpful to avoid things that make your skin dry, such as too much central heating, and soap. Your doctor can prescribe creams to moisturise your skin.

To reduce scaly or flaky skin it is helpful to moisturise the skin and also avoid things that make you go red.

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

Nausea (feeling sick) and less commonly vomiting. There are now very effective anti-sickness drugs to prevent or greatly reduce this effect. 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 information on managing nausea and vomiting.

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

Fever may occur. If your temperature goes above 38°C (100.5°F), contact your doctor or the hospital straight away.

Less common side effects

Allergic reactions. Signs of a reaction include skin rashes and itching, a feeling of swelling in the tongue or throat, irritation of the nasal passages, wheezing, a cough and breathlessness. You will be monitored closely during your treatment, but tell your nurse or doctor if you have any of these symptoms. To reduce the chance of developing an allergic reaction, certain drugs (antihistamines) can be given before the infusion. The drip can also be slowed down or stopped until the reaction is over.

Headaches. If you have headaches, let you doctor know.

Sore mouth. 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 reduce the risk of this happening. Tell your doctor if you do have any of these problems. Special mouthwashes and medicines can be prescribed to prevent or clear any mouth infection.

Constipation. Your doctor can prescribe laxatives if constipation occurs.

Lowered resistance to infection Cetuximab can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This is rare if cetuximab is given on its own.

Contact your doctor or the hospital straightaway if:

  • Your temperature goes above 38°C (100.5°F)
  • You suddenly feel unwell (even with a normal temperature)

CancerBACUP has information on how to avoid infection when you have reduced immunity, which you may find helpful.

Anaemia (low number of red blood cells) While having treatment with cetuximab you may become anaemic. This may make you feel tired and breathless. Let your doctor know if you feel tired or breathless or are very pale.

Tiredness and weakness Some people feel weak and tired, and as though they have no strength while having treatment with cetuximab. This gradually disappears once the treatment is finished.

Aching or pain in the muscles or bones can usually be controlled with mild painkillers which your doctor can prescribe.

Your liver may be temporarily affected Cetuximab may cause changes in the way that your liver works, which go back to normal when the treatment is finished. This is very unlikely to cause you any harm, but your doctor will monitor this carefully. Samples of your blood will be taken from time to time to check your liver function.

Additional information

Cetuximab is not given to people who are allergic to mice.

References

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

  • Website of the American Cancer Society – www.cancer.org
  • BASELGA, J (2001) The EGFR as a target for anticancer therapy – focus on cetuximab. European Journal Of Cancer. 37, S16-S22.
  • Robert F et al (2001) Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. Journal Of Clinical Oncology. 19 (13), p3234-3243.
  • McCarthy M (2003) Anti-angiogenesis drug promising for metastatic colorectal cancer. The Lancet. 361 (June 7), p1959/
  • Mendelson J and Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. Journal Of Clinical Oncology. 21 (14), p2787-2799.
  • Ransom M and Sliwkowski M X (2002). Perspectives on anti-HER monoclonal antibodies. Oncology. 63 (supplement 1), p17-24

For further references, please see the general bibliography.

Alemtuzumab (MabCampath®)

What is alemtuzumab?

Alemtuzumab is one of a new group of cancer drugs known as monoclonal antibodies. It is mainly used to treat people with B-cell chronic lymphocytic leukaemia (CLL). It is sometimes used as part of research trials to treat other types of leukaemia. Currently alemtuzumab is usually given to people whose CLL has come back after previous treatment or if it is not responding to chemotherapy.

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, the side effects the drug may cause and which cancers it may be used to treat. The trials also find out how effective the drug is, and whether it is better than the existing treatments or has extra benefit when given with these drugs.

What is a monoclonal antibody?

Monoclonal antibodies are used to try to destroy some types of cancer cells while causing little harm to normal cells. They recognise certain proteins that are found on the surface of some types of cancer cells. The monoclonal antibody recognises the protein and locks on to it (like a key in a lock). This may then trigger the body’s immune system to attack the cancer cells and cause the cells to destroy themselves.

Alemtuzumab locks on to a protein called CD52. This is found on the surface of certain white blood cells (lymphocytes), including those affected by the leukaemia. The leukaemic lymphocytes are known as malignant lymphocytes. Alemtuzumab attacks both malignant and normal lymphocytes. However the body quickly replaces any normal white blood cells that are damaged, so the risk of side effects from the treatment is small.

What it looks like

Alemtuzumab is a clear fluid after being diluted.

How is it given

Alemtuzumab is given as a drip (infusion) through a fine tube (cannula) inserted into a vein in the arm or back of the hand. Each drip takes approximately two hours.

Some people have an allergic reaction to alemtuzumab. To reduce the risk of a reaction the first few doses are given slowly. You may also be given some antihistamines, paracetamol and sometimes a small dose of steroids before the infusion. These will help to reduce the risk of reactions. If you do have a reaction, the infusion can be stopped and started again once the symptoms are over.

You will be asked to stay in hospital for a few hours after the infusion, or possibly overnight, to be monitored. The dose of alemtuzumab is increased over a few days until the recommended dose is achieved. This usually takes 3–7 days and is known as dose escalation. Once the recommended dose is achieved the treatment is given three times a week (e.g. on Monday, Wednesday and Friday). Most people have treatment for 4–12 weeks.

Side effects

Each person’s reaction to a cancer drug is unique. Some people have very few side effects, while others may experience more. We have outlined the commonest side effects, so that you can be aware of them if they occur. However, we have not included those which 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.

Most side effects of alemtuzumab fall into two groups:

  • early side effects – those which occur during or immediately after the drug has been given (which include allergic-type reactions)
  • later side effects – tthose which occur after a few weeks of treatment, of which the main one is infection.

Early side effects

Allergic reactions It is common to have a slight allergic reaction to alemtuzumab, although some people have a more severe reaction. Signs of a reaction include skin rashes and itching, a feeling of swelling in the tongue or throat, irritation of the nasal passages, wheezing, a cough and breathlessness. You will be monitored closely during your treatment but it is very important to tell your nurse or doctor if you have any of these symptoms.

To reduce the chance of developing an allergic reaction certain drugs (antihistamines) are given before the infusion. The infusion can also be slowed down or stopped until the reaction is over. Generally the reaction gets better within a few hours, once the treatment has ended, and is almost always more severe with the first few doses of alemtuzumab.

Flu-like symptoms  This can include a high temperature and chills, weakness, sweating, muscle aches, tiredness, dizziness and headaches. These effects can occur while the drug is being given, but do not usually last long.

Feeling sick (nausea) and occasional vomiting  There are now very effective anti-sickness drugs to prevent or substantially reduce this. If the sickness is not controlled, or continues, let your doctor know so that he or she can prescribe other anti-sickness drugs which may be more effective.

Low blood pressure  This may happen during the infusion, so your blood pressure will be regularly checked. People who normally take medicines to lower their blood pressure need to discuss with their doctor whether any adjustments should be made to their usual medicines during this time.

Later side effects

After a few weeks of treatment the following effects may occur.

Reduction in white blood cells  Healthy white cells fight off infection and so alemtuzumab may increase your risk of developing infections. This risk is usually at its highest whilst you are having the treatment and for about two months afterwards. It is recommended that antibiotic and antiviral medication is taken during alemtuzumab treatment and for at least two months afterwards. In some people the production of white blood cells by the bone marrow may be reduced for up to a year following treatment.

Problems with blood clotting  This is caused by a reduction in the production of platelets by the bone marrow. It may lead to an increased risk of bleeding, although this usually only lasts a short time. You will have your blood checked regularly to monitor this.

Less common side effects

You may also have diarrhoeaabdominal painsskin rashesbreathlessness or a cough. Let your doctor or nurse know if you have any of these so that effective treatment can be prescribed.

Additional Information

Alemtuzumab may worsen heart problems in people who already have them. For this reason it will be used with caution if you have had heart disease.

It is unknown what effect alemtuzumab may have on an unborn baby. It is recommended that women able to become pregnant, and men who are sexually active, use effective birth control whilst having alemtuzumab and for at least one year after the treatment has ended. It is recommended that women should not breastfeed during the treatment and for at least four weeks afterwards.

References

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

  • Martindale: The Complete Drug Reference (33rd edition). Sweetman et al. Pharmaceutical Press, 2002.
  • British National Formulary (46th edition). British Medical Association and Royal Pharmaceutical Society of Great Britain, September 2003.

For further references, please see the general bibliography.

ADEPT (Antibody Directed Enzyme Pro-drug Therapy)

Drugs in development

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, the side effects that the drug may cause and which cancers it may be used to treat. The trials also find out how effective the drug is, and whether it is better than the existing treatments, or has extra benefit when given with these drugs.

Many drugs that are thought to be promising may be found not to be as good as 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 who is taking one of these developmental drugs. If you are having a developmental drug 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.

 

ADEPT

ADEPT (Antibody-Directed Enzyme Pro-drug Therapy) is a new type of cancer treatment that involves a group of drugs called monoclonal antibodies. At the moment ADEPT is being used only in clinical trials. The trials aim to find out whether ADEPT may be useful as a new type of treatment for bowel cancer in the future.

 

What is a monoclonal antibody?

Monoclonal antibodies recognise certain proteins that are found on the surface of some cancer cells. They are used to try to destroy the cancer cells, while causing little harm to normal cells.

The monoclonal antibody recognises the protein on the surface of the cancer cell and locks on to it (like a key in a lock). Some monoclonal antibodies can then trigger the body’s immune system to attack the cancer cells and can also cause the cells to destroy themselves.

Sometimes monoclonal antibodies have a cancer drug or radioactive substance attached to them. They can be used in this way to deliver treatment directly to the cancer cell which is known as targeted therapy.

 

How does ADEPT work?

ADEPT is a type of targeted therapy. It uses a monoclonal antibody to carry an enzyme directly to the cancer cells. A few hours after the monoclonal antibody is given (with the enzyme attached) a pro-drug is given. The pro-drug is an inactive anti-cancer drug. When this pro-drug comes into contact with the enzyme, which is now attached to the cancer cell, a reaction takes place which activates the anti­cancer drug. The anti-cancer drug is then able to destroy the cancer cells. As normal cells do not have the antibody with the enzyme the treatment does not affect them.

 

What it looks like

ADEPT is a clear fluid.

 

How it is given

ADEPT is given by a drip (infusion) into the vein through a small tube (cannula) inserted into the vein. It is usually given in two separate doses on the same day.

 

Possible side effects

Trials are looking at the side effects that may occur. As ADEPT is still a relatively new treatment it is too early to know all of the possible side effects. However, the following appear to be the most common.

Flu-like symptoms  These may include fever and chills, headaches, itching and joint and muscle aches. These may occur a few hours after the drug is given, but do not last for more than a day or two.

Allergic reaction  Signs of an allergic reaction include skin rashes and itching, high temperatures, shivering, redness of the face, dizziness, a headache, breathlessness, anxiety and a need to pass urine.

You will be monitored for any sign of an allergic reaction during your treatment. Tell your doctor or nurse if you have any of these signs. Before you receive your treatment you will be given medication to reduce the chances of an allergic reaction.

Increased risk of infection  A temporary reduction in your white blood cells can occur a few days after the treatment is given. If this happens you are more likely to get an infection during this period. Your doctor or nurse will advise you about this and any precautions that you should take. Your white cells usually recover in three to four weeks.

Nausea (feeling sick) and vomiting  There are now very effective anti-sickness drugs to prevent or greatly reduce nausea and vomiting. If it does happen it may begin a few hours after the drug has been given, and may last for a few days. If the sickness is not controlled, or continues, tell your doctor. He or she can prescribe other anti-sickness drugs which may be more effective.

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

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References

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

  • Martindale: The Complete Drug Reference (33rd edition). Sweetman et al. Pharmaceutical Press, 2002.
  • British National Formulary (46th edition). British Medical Association and Royal Pharmaceutical Society of Great Britain, September 2003.

For further references, please see the general bibliography.