This information is about a new treatment called tositumomab, commonly known as BEXXAR®. It is being tested as a treatment for people with certain types of non-Hodgkin lymphoma.

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

At this stage, BEXXAR is only available to a small number of people in the UK, usually 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 is a type of monoclonal antibody. At the moment it is used only in clinical trials to treat certain types of B-cell non-Hodgkin lymphoma (NHL) that have come back after previous treatment.

Monoclonal antibodies are used to try to destroy cancer cells, while causing little harm to normal cells. They do this by recognising certain proteins found on the surface of cancer cells and 'locking' onto them (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 make the cells 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.

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

BEXXAR is given as a drip (infusion), 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 1–2 weeks. The first three visits are needed to decide how much radioactivity you will be given and the fourth will actually be for the treatment.

Before you start treatment, and for two weeks after you are given the 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 side effects. The first drip is an infusion of the monoclonal antibody without any radioactive iodine. It 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 Iodine-131. 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 to you. Soon after this second infusion you will have the first of three body scans. These take between 15–30 minutes and show how much radioactivity is still in the body and where it is.

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

The third visit on day six or seven 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 seven and 14) is when you actually have the treatment dose of BEXXAR. You will have two infusions through your cannula: the first one of just the monoclonal antibody, over an hour; and the second containing the dose of radioactive antibody, 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 in 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.

BEXXAR is still a relatively new drug so it is too early to know all about the possible side effects. Those listed below appear to be the most common.

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 (antihistamines) can be given before the infusion. If a reaction does occur the BEXXAR infusion can be slowed down or stopped until the reaction is over.

Flu-like symptoms These may include fever and chills, sweating, 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.

Lowered resistance to infection BEXXAR can reduce the production of white blood cells by the bone marrow, making you more prone to infection. Your resistance to infection usually reaches its lowest point 4–7 weeks after the first dose of BEXXAR and lasts for about a month. Your blood cells will then increase steadily and will usually have returned to normal levels over several weeks.

Contact your doctor or the hospital straightaway if:

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

You will have regular blood tests to check your blood cell count.

Bruising or bleeding BEXXAR can also reduce the number of platelets (which help the blood to clot). Let your doctor know if you notice any abnormal bruises or bleeding.

Anaemia (low number of red blood cells) You may become anaemic if the amount of your red cells is low. Your doctor or nurse will advise you about this and any precautions you should take. The blood cells usually recover in 3–4 weeks.

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

There is a very small risk that BEXXAR may cause a second cancer to develop. Your doctor should discuss this risk with you.

Effects of radioiodine treatment It may be advisable to stay up to two metres away from others (particularly children) when your dose is still high. Some people should avoid having sexual intercourse for some time after treatment and you should not conceive or father a child for one year after taking BEXXAR. These times can change depending on the dose of radiation given and may also vary according to hospital guidelines. Your doctor will be able to give you more information. Patients who travel by air may set off radiation detectors at airports for some weeks after treatment. You may be questioned by security staff, and so it is a good idea to have a doctor's letter which explains that you have recently had radioactive iodine treatment.

If you have any questions about these or any other side effects, you can 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 you are having.

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.