Immunologic therapies



Definition

Immunologic therapy is an approach to the treatment of disease that uses medicines for stimulating the body's natural immune response.


Purpose

Immunologic therapy is used to improve the immune system's natural ability to fight such diseases as cancer, hepatitis, and AIDS. These drugs may also be used to help the body recover from immunosuppression resulting from such treatments as chemotherapy or radiation therapy.


Description

Most drugs in this category are synthetic versions of substances produced naturally in the body. In their natural forms, these substances help defend the body against disease. For example, aldesleukin (Proleukin) is an artificial form of interleukin-2, which helps white blood cells work. Aldesleukin is administered to patients with kidney cancers and skin cancers that have spread to other parts of the body. Filgrastim (Neupogen) and sargramostim (Leukine) are versions of natural substances called colony stimulating factors, which encourage the bone marrow to make new white blood cells. Another type of drug, epoetin (Epogen, Procrit), is a synthetic version of human erythropoietin, which stimulates the bone marrow to make new red blood cells. Thrombopoietin stimulates the production of platelets, which are disk-shaped bodies in the blood that are important in clotting. Interferons are substances that the body produces naturally, using cells in the immune system to fight infections and tumors. Synthetic interferons carry such brand names as Alferon, Roferon or Intron A. Some of the interferons that are currently in use as medications are recombinant interferon alfa-2a, recombinant interferon alfa-2b, interferon alfa-n1, and interferon alfa-n3. Alfa interferons are used to treat hairy cell leukemia, malignant melanoma, and Kaposi's sarcoma, which is a type of cancer associated with HIV infection. In addition, interferons are also used to treat such other conditions as laryngeal papillomatosis, genital warts, and certain types of hepatitis.


Recommended dosage

The recommended dosage depends on the type of immunologic therapy. For some medicines, the physician will decide the dosage for each patient, taking into account a patient's weight and whether he or she is taking other medicines. Some drugs used in immunologic therapy are given only in a hospital under a physician's supervision. Patients who are taking drugs that can be used at home should consult the physician who prescribed the medicine or the pharmacist who filled the prescription for the correct dosage.

Most of these drugs come in an injectable form, which is generally administered by a cancer care provider.


Precautions

Aldesleukin

This drug may temporarily increase the patient's risk of getting infections. It may also lower the number of platelets in the blood, and thus interfere with the blood's ability to clot. Taking the following precautions may reduce the chance of such complications:

Aldesleukin may make some disorders worse, including chickenpox, shingles (herpes zoster), liver disease, lung disease, heart disease, underactive thyroid, psoriasis, immune system problems and mental problems. The medicine may also increase the risk of seizures (convulsions) in people with epilepsy or other seizure disorders. In addition, the drug's effects may be intensified in people with kidney disease, because their kidneys are slow to clear the medicine from their bodies.


Colony stimulating factors

Certain drugs used in treating cancer reduce the body's ability to fight infections. Although colony stimulating factors help restore the body's natural defenses, the process takes time. Getting prompt treatment for infections is important, even while the patient is taking these medications. Patients taking colony stimulating factors should call their physician at the first sign of illness or infection, including a sore throat, fever, or chills.

People with certain medical conditions may have problems if they take colony stimulating factors. Patients with kidney disease, liver disease, or conditions related to inflammation or immune system disorders may find that colony stimulating factors make their disorder worse. People with heart disease may be more likely to experience such side effects as water retention and irregular heart rhythm while taking these drugs. Patients with lung disease may increase their risk of shortness of breath. People with any of these medical conditions should consult their personal physician before using colony stimulating factors.


Epoetin

Epoetin is a medicine that may cause seizures (convulsions), especially in people with epilepsy or other seizure disorders. No one who takes epoetin should drive, operate heavy machinery, or do anything that would be dangerous to themselves or others in the event of a seizure.

Epoetin helps the body make new red blood cells, but it is not effective unless there are adequate stores of iron in the body. The patient's physician may recommend taking iron supplements or certain vitamins that help to maintain the body's iron supply. It is necessary to follow the physician's advice in this instance, as with any dietary supplements that should come only from a physician.

Studies of laboratory animals indicate that epoetin taken during pregnancy causes birth defects in these species, including damage to the bones and spine. The drug, however, has not been reported to cause problems in human babies whose mothers took it during pregnancy. Nevertheless, women who are or may become pregnant should check with their physicians for the most upto-date information on the safety of taking this medicine during pregnancy.

People with certain medical conditions may have problems if they take epoetin. For example, there appears to be a greater risk of side effects in people with high blood pressure, disorders of the heart or blood vessels, or a history of blood clots. In addition, epoetin may not work properly in people who have bone disorders or sickle cell anemia.


Interferons

Interferons may intensify the effects of alcohol and other drugs that slow down the central nervous system, including antihistamines, over-the-counter cold medicines, allergy medications, sleep aids, anticonvulsants, tranquilizers, some pain relievers, and muscle relaxants . Interferons may also intensify the effects of anesthetics, including the local anesthetics used for dental procedures. Patients taking interferons should consult their physicians before taking any of the medications listed above.

Some people experience dizziness, unusual fatigue, or drowsiness while taking these drugs. Because of these possible problems, anyone who takes these drugs should not drive, use heavy machinery, or do anything else that requires full alertness until they have determined how the drugs affect them.

Interferons often cause flu-like symptoms, including fever and chills. The physician who prescribes this medicine may recommend taking acetaminophen (Tylenol) before—and sometimes after—each dose to keep the fever from getting too high. If the physician recommends taking acetaminophen, the patient should follow his or her instructions carefully.

Like aldesleukin, interferons may temporarily increase the risk of getting infections and lower the number of platelets in the blood, which may lead to clotting problems. Patients should observe the precautions listed above for reducing the risk of infection and bleeding for aldesleukin.

People who have certain medical conditions may have problems if they take interferons. For example, the drugs may worsen some medical conditions, including heart disease, kidney disease, liver disease, lung disease, diabetes, bleeding problems, and certain psychiatric disorders. In people who have overactive immune systems, these drugs can even increase the activity of the immune system. People who have shingles or chickenpox, or who have recently been exposed to chickenpox, may increase their risk of developing severe problems in other parts of the body if they take interferons. People with a history of seizures or associated mental disorders may be at risk if they take interferon.

Elderly people appear to be at increased risk of side effects from taking interferons.

Interferons may cause changes in the menstrual cycles of teenagers. Young women should discuss this possibility with their physicians. These drugs are not known to cause fetal death, birth defects, or other problems in humans when taken during pregnancy. Women who are pregnant or who may become pregnant should ask their physicians for the latest information on the safety of taking these drugs during pregnancy.

Women who are breastfeeding their babies may need to stop while taking this medicine. It is not yet known whether interferons pass into breast milk; however, because of the chance of serious side effects that might affect the baby, women should not breastfeed while taking interferon. Patients should consult their physician for more specific advice.


General precautions for all types of immunologic therapy

Regular appointments with the doctor are necessary during immunologic therapy treatment. These checkups give the physician a chance to make sure the medicine is working and to monitor the patient for unwanted side effects.

Anyone who has had unusual reactions to the drugs used in immunologic therapy should inform the doctor before resuming the drugs. Any allergies to foods, dyes, preservatives, or other substances should also be reported.


Side effects

Aldesleukin

Aldesleukin may cause serious side effects. It is ordinarily given only in a hospital, where medical professionals can watch for early signs of problems. Medical tests may be performed to check for unwanted side effects. In general, anyone who has breathing problems, fever or chills while being given aldesleukin should consult their doctor at once.

Other side effects should be brought to a physician's attention as soon as possible:

Some side effects of aldesleukin are usually temporary and do not need medical attention unless they are bothersome. These include dry skin, itchy or burning rash or redness followed by peeling, loss of appetite, and a general feeling of illness or discomfort.


Colony stimulating factors

Patients sometimes experience mild pain in the lower back or hips in the first few days of treatment with colony stimulating factors. This side effect is not a cause for concern, and usually goes away within a few days. If the pain is intense or causes discomfort, the physician may prescribe a painkiller.

Other possible side effects include headache, joint or muscle pain, and skin rash or itching. These side effects tend to disappear as the body adjusts to the medicine, and do not need medical treatment. If they continue, or if they interfere with normal activities, the patient should consult their physician.


Epoetin

Epoetin may cause such flu-like symptoms as muscle aches, bone pain, fever, chills, shivering, and sweating within a few hours after it is taken. These symptoms usually go away within 12 hours. If they persist or are severe, the patient should call their doctor. Other possible side effects of epoetin that do not need medical attention are diarrhea, nausea or vomiting, and fatigue or weakness.

Other side effects, however, should be brought to a physician's attention as soon as possible. These include headache; vision problems; a rise in blood pressure; fast heartbeat; weight gain; or swelling of the face, fingers, lower legs, ankles, or feet. Anyone who has chest pain or seizures after taking epoetin should seek professional emergency medical attention immediately.


Interferons

Interferons may cause temporary hair loss (alopecia). Although this side effect may be upsetting because it affects the patient's appearance, it is not a sign that something is seriously wrong. The hair should grow back normally after treatment ends.

As the body adjusts to these medications, the patient may experience other side effects that usually go away during treatment. These include flu-like symptoms, alterations in the sense of taste, loss of appetite (anorexia), nausea and vomiting, skin rashes, and unusual fatigue. The patient should consult a doctor if these problems persist or if they interfere with normal life.

Other side effects are more serious and should be brought to a physician's attention as soon as possible:

General precautions regarding side effects for all types of immunologic therapy

Other side effects are possible with any type of immunologic therapy. Anyone who has unusual symptoms during or after treatment with these drugs should contact the physician immediately.


Interactions

Anyone who has immunologic therapy should give their physician a list of all other medications that they take, including over-the-counter and herbal preparations. Some combinations of drugs may increase or decrease the effects of one or both drugs, or increase the likelihood of side effects.


Alternatives

Immunoprevention

Immunoprevention is a form of treatment that has been proposed as a form of cancer therapy. There are two types of immunoprevention, active and passive. Treatment that involves such immune molecules as cytokines, which are prepared synthetically, or other immune molecules that are not produced by patients themselves are called passive immunotherapy. By contrast, vaccines are a form of active immune therapy because they elicit an immune response from the patient's body. Cancer vaccines may be made of whole tumor cells or from substances or fragments from the tumor known as antigens.


Adoptive immunotherapy

Adoptive immunotherapy involves stimulating T lymphocytes by exposing them to tumor antigens. These modified cells are grown in the laboratory and then injected into patients. Since the cells taken from a different person for this purpose are often rejected, patients serve both as donor and recipient of their own T cells. Adoptive immunotherapy is particularly effective in patients who have received massive doses of radiation and chemotherapy. In such patients, therapy results in immunosuppression (weakened immune systems), making them vulnerable to viral infections. For example, CMV-specific T cells can reduce the risk of cytomegalovirus (CMV) infection in organ transplant patients.


Resources

books

"Factors Affecting Drug Response: Drug Interactions." In The Merck Manual of Diagnosis and Therapy , edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Reiger, Paula T. Biotherapy: A Comprehensive Overview . Sudbury: Jones and Bartlett, Inc. 2000.

Stern, Peter L., P. C. Beverley, and M. Carroll. Cancer Vaccines and Immunotherapy . New York: Cambridge University Press, 2000.

Wilson, Billie Ann, RN, PhD, Carolyn L. Stang, PharmD, and Margaret T. Shannon, RN, PhD. Nurses Drug Guide 2000 . Stamford, CT: Appleton and Lange, 1999.

periodicals

"Immunoprevention of Cancer: Is the Time Ripe?" Cancer Research 60 (May 15, 2000): 2571-2575.

Rosenberg, S. A. "Progress in the Development of Immunotherapy for the Treatment of Patients with Cancer." Journal of Internal Medicine 250 (December 2001): 462-475.

Rosenberg, S. A. "Progress in Human Tumor Immunology and Immunotherapy." Nature 411 (May 17, 2001): 380-385.

organizations

American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000. http://www.ashp.org .

National Cancer Institute (NCI). NCI Public Inquiries Office, Suite 3036A, 6116 Executive Boulevard, MSC8332, Bethesda, MD 20892-8322. (800) 4-CANCER or (800) 332-8615 (TTY). http://www.nci.nih.gov .

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA. http://www.fda.gov .

other

National Cancer Institute (NCI). Treating Cancer with Vaccine Therapy . http://www.cancertrials.nci.nih.gov/news/features/vaccine/html/page05.htm .


Nancy Ross-Flanigan
Samuel Uretsky, PharmD
Kausalya Santhanam, Ph.D.



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