How Rheumatologists Use Chemotherapy

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Revmatiukerforbund

What is chemotherapy? In cancer treatment, chemotherapy refers to the use of any of a group of drugs whose main effect is either to kill or slow the reproduction of rapidly multiplying cells. In rheumatology, chemotherapy is designed to decrease the abnormal behavior of cells, rather than kill cells. The doses of medicine used for rheumatic or autoimmune conditions are lower than the doses used for cancer treatment.

How does chemotherapy help treat inflammatory and autoimmune diseases?
In many rheumatic diseases, inflammation causes damage to parts of the body, such as the joints in rheumatoid arthritis. In many cases, inflammation results from autoimmunity. Autoimmunity is a malfunction of the immune system in which one’s own tissues or organs are misinterpreted as being foreign and become the object of “attack.”

Chemotherapy slows cell reproduction and decreases certain products made by these cells and thus might help people with certain inflammatory and autoimmune diseases. Because of the suppressive effect of chemotherapy on autoimmunity, these drugs are sometimes called immunosuppressive drugs.

Disease modifying drugs is another name collectively given to the chemotherapy drugs used to treat rheumatic diseases. They are different from anti-inflammatory drugs or pain medicines, which work right away, provide only short-term relief, and do not improve long-term disease outcome. Chemotherapy drugs take longer to have a complete effect, sometimes several weeks or up to a few months. Because they alter the immune response that causes the disease, they can slow down significantly and sometimes stop the course of the rheumatic disease for which they are prescribed.

What chemotherapy drugs do rheumatologists use?
Although there are many chemotherapy drugs, only a handful have widespread use in treating rheumatic diseases today. These are:

  • Methotrexate (Rheumatrex)
  • Azathioprine (Imuran)
  • Cyclophosphamide (Cytoxan)
  • Leflunomide (Arava)
  • Mycophenolate mofetil (CellCept)

Methotrexate
Methotrexate is the chemotherapeutic drug most widely used by rheumatologists for two main reasons: It is effective in treating rheumatoid arthritis and certain other rheumatic diseases (especially polymyositis and certain types of vasculitis – inflammation of blood vessels), and it is relatively safe.

It is due to methotrexate and to other newer drugs available today that the outcome of rheumatoid arthritis has improved in the past decade.

Most patients can take methotrexate by mouth in a single, once-a-week dose. Some patients prefer to take it as an injection once a week.

Azathioprine
Azathioprine has been used for many years as an immunosuppressive drug to prevent graft rejection in patients receiving kidney transplants. It is also used to suppress the abnormal immune response in some patients with systemic lupus erythematosus (lupus), rheumatoid arthritis, and vasculitis.

It is usually taken in a single daily dose by mouth.

Cyclophosphamide
Cyclophosphamide is considerably more powerful and toxic than methotrexate and azathioprine. It is used to treat the most aggressive and dangerous rheumatic diseases, such as severe lupus and some forms of vasculitis. In such instances, cyclophosphamide is a life-saving treatment.

Cyclophosphamide directly attacks the components of the cell nucleus that contain the genes – the nucleic acids – interfering with the production of certain proteins. Although rapidly reproducing cells are more susceptible to this action than resting cells, any cell can be affected if there is enough drug present.

Cyclophosphamide is taken either by mouth or by injection.

Leflunomide
Leflunomide is another drug used to treat rheumatoid arthritis. It is comparable to methotrexate in its ability to control disease activity in rheumatoid arthritis. It disrupts the production of deoxyribonucleic acid (DNA), thereby interfering with the immune cells that play a role in the development of rheumatoid arthritis.

Leflunomide is taken by mouth, once a day.

Mycophenolate mofetil
Mycophenolate was originally used to treat patients with organ transplants but now it is sometimes used in the treatment of some autoimmune diseases such as lupus or vasculitis.

Mycophenolate targets an enzyme in the body called inosine monophosphate dehydrogenase, which is important for the formation of deoxyribonucleic acid (DNA) in cells. By interfering with DNA, the medicine impairs function of immune system cells that become overactive in autoimmune diseases such as lupus.

Mycophenolate is taken by mouth, twice a day.

What kind of side effects do these drugs have?
Side effects of chemotherapeutic drugs are fairly common, even though the doses are typically lower than the doses used to treat cancer.

Some patients might experience an upset stomach, nausea, vomiting, or diarrhea while on chemotherapy. These symptoms might go away with time, but tell your doctor if they persist.

All of these drugs can diminish the formation of blood cells, resulting in:

  • Anemia (low red blood cell count)
  • Low white blood cell count that might cause decreased resistance to infection
  • Low platelet count that might cause impaired blood clotting

In addition, methotrexate, azathioprine, and leflunomide can damage the liver, and cyclophosphamide can damage the urinary bladder lining and cause bleeding or cancer in the bladder lining. Cyclophosphamide also causes hair loss and sterility.

Methotrexate and cyclophosphamide can damage the lungs.

Women who are pregnant or plan to become pregnant should not take these medicines. Use a birth control method that you can trust. If you are pregnant, tell your doctor right away.

As a general rule, elderly patients and those with chronic medical problems such as liver disease or renal disease might be more likely to experience side effects from chemotherapy. Dosing adjustments and more frequent monitoring might be necessary.

Immunosuppressive drugs diminish your body’s ability to fight infections. Let your doctor know right away if you experience a fever or other signs of infection, and stay up to date with your vaccinations.

Some chemotherapy drugs have been associated with a slight increased risk of cancer.

Be sure to tell your doctor about other medicines you are taking, including over-the-counter drugs or other remedies, as they could increase the risk of side effects or interfere with the effectiveness of the drugs prescribed for you.

Since no drug is entirely safe, your rheumatologist will talk to you about the possible benefits of these drugs, as well as their side effects. The occurrence of side effects depends on the dose, type of medicine, and length of treatment.

Obviously, it is very important to have the appropriate follow-up examinations and laboratory testing while taking chemotherapeutic drugs. Careful monitoring can minimize all of these risks.

How fast do chemotherapeutic drugs work?
Although there are some differences among the drugs and how they are used to treat certain rheumatologic and autoimmune diseases, these drugs usually produce benefits gradually, requiring weeks to months for full effectiveness.

Methotrexate and azathioprine can be used for prolonged periods (many years) if necessary, as long as they do not cause side effects.

Cyclophosphamide is preferably used for more limited periods of time because of its greater toxicity. However, in certain cases more prolonged use might be necessary.

Generally, if there is no benefit within four months, it is unlikely that continuing the chemotherapeutic drug at the same dose will be helpful.

For more information
The information provided above is designed to give you a general overview. For more detailed information, the following websites might be useful:

American College of Rheumatology:
http://www.rheumatology.org/public/factsheets/

National Institutes of Health Medline Plus:

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