Fever

Normal human body temperature changes during each 24-hour period according to a definite pattern. It is lowest in the morning before dawn and highest in the afternoon. Normal body temperature is maintained by temperature control activities in the body that keep a balance between heat loss and heat production.

An abnormal increase in body temperature is caused by either hyperthermia (an unusual increase in body temperature above normal) or fever. Hyperthermia is caused by a breakdown in the body's temperature control activities. In fever, the temperature controls in the body are working correctly, but body temperature increases as the body responds to chemicals produced by microorganisms that cause infection or works to kill harmful microorganisms such as bacteria or viruses. There are three phases to fever. In the first phase, the body raises its temperature to a new level by causing the blood vessels in the skin to constrict and move blood from the skin surface to the interior of the body which helps to retain heat. The skin becomes cool, the muscles contract causing shivering or chills, and the body produces more heat. The body's efforts to retain and produce heat continue until a new higher temperature is reached. In the second phase, heat production and heat loss are equal, shivering stops, and the body maintains the new higher temperature. In the third phase, body temperature is lowered to normal as the body gets rid of the excess heat by causing the blood vessels in the skin to open and move blood from the interior of the body to the skin surface. Sweating occurs and helps to cool the body.

Fever is most likely to cause harmful effects in older persons or the very young. In older persons, the hypothalamus' temperature regulating centers do not work as well and the body temperature may rise above normal causing irregular heartbeat, lack of blood flow, changes in the ability to think clearly, or heart failure. Children between 6 months and 6 years old may have seizures due to a fever.

The main causes of fever in cancer patients are infections, tumors, reactions to drugs or blood transfusions, and graft-versus-host-disease. Graft-versus-host-disease occurs when transplanted bone marrow or peripheral stem cells attack the patient's tissue. Infection is a common cause of fever in cancer patients and can cause death. Tumor cells can produce various substances that can cause fever. A wide variety of medications can cause fever including chemotherapy drugs, biological response modifiers, and antibiotics, such as vancomycin and amphotericin.

Other causes of fever in cancer patients include drug withdrawal; neuroleptic malignant syndrome; blockages of the bladder, bowel, or kidney, and blockage of an artery by tumor fragments. Other medical conditions occurring at the same time as the cancer such as blood clots, connective tissue disorders, and central nervous system hemorrhage or stroke, may also cause fever.

The doctor will ask questions about past medical problems, review all medications the patient is taking, and perform a thorough physical examination to determine the cause of fever. Patients who are suspected of having an infection, especially those who have neutropenia (a very low white blood cell count) and fever, will undergo very careful inspection of the skin, body openings (mouth, ears, nose, throat, urethra, vagina, rectum), needle stick sites, biopsy sites, and skin folds (for example, the breasts, armpits, or groin). The teeth, gums, tongue, nose, throat, and sinuses will be carefully examined. Any tubes that are inserted into veins or arteries or other tubes placed in the body, such as stomach tubes, are common sources of infection. Urine, sputum, and blood specimens will be examined for signs of infection. Patients with neutropenia may not show the usual symptoms of infection, so they should be examined frequently.

The symptoms of fever in very weakened cancer patients may include fatigue, muscle pain, sweating, and chills. Possible treatments to manage fever include those that treat the underlying cause, giving intravenous fluids, nutritional support, and other measures to make the patient more comfortable. The specific treatments are determined by the stage of cancer and the patient's goals for care. For example, some patients who are nearing the end of life may decide not to be treated for the underlying cause such as pneumonia or other infections, but may still request general comfort measures and fluids to maintain their quality of life. Other patients may choose antibiotics to relieve symptoms such as cough, fever, or shortness of breath that occur because of the infection. See the General Treatments to Relieve Fever ¹ section of this summary for more information.

Antibiotics may be used to treat fever caused by infection. Antibiotic therapy regimens and drugs to treat fungal infections are prescribed by the doctor. Fever caused by a tumor is usually treated by prescribing standard therapies for the specific type of cancer. If the therapy is not successful, the therapy takes awhile to work, or there is no therapy available, the doctor may prescribe nonsteroidal anti-inflammatory drugs (NSAIDs).

Sometimes fever may be caused by a reaction to drugs given to treat the cancer or prevent infection. Drugs that are known to cause fever include biological response modifiers, amphotericin B, and bleomycin. Suspected drug-related fever may be treated by stopping the drug that is causing the fever. When a biological response modifier, certain chemotherapy drugs, or antibiotics cause the fever, the doctor may control the fever by adjusting the type of drug, how the drug is given, the amount of drug given, or how often the drug is given. Acetaminophen, NSAIDs, and steroids may also be given before the patient receives the drug that causes the fever. Meperidine may be given to stop chills associated with a drug-related fever.

Neuroleptic malignant syndrome (NMS) is a rare but sometimes fatal reaction to drugs that a patient is given for psychotic conditions, delirium, or nausea and vomiting. The symptoms of NMS are fever, muscle stiffness, confusion, loss of control of body functions, and an increase in white blood cell count. A delirious patient who does not improve when treated with medication should be examined for NMS. Treatment for NMS includes stopping the drug, treating the symptoms, and sometimes using other drugs. (Refer to the PDQ summary on Cognitive Disorders and Delirium ² for more information.)

Cancer patients may develop a fever as a reaction to blood products (for example, receiving a blood transfusion). Removing white blood cells from the blood or treating the blood product with radiation before transfusing it into the patient can lessen the reaction. The possibility of fever due to receiving blood products can also be lessened by giving patients acetaminophen or antihistamines before the transfusion.

Along with treatment of the underlying cause of fever, comfort measures may also be helpful in relieving the discomfort that goes along with fever, chills, and sweats. During periods of fever, giving the patient plenty of liquids, removing excess clothing and linens, and bathing or sponging the patient with lukewarm water may give relief. During periods of chills, replace wet blankets with warm, dry blankets, keep the patient away from drafts, and adjust the room temperature to improve patient comfort.

Nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen may also be prescribed to relieve symptoms. Aspirin may be effective in decreasing fever, but should be used with caution in patients with Hodgkin lymphoma and cancer patients who are at risk for developing a decrease in the number of platelets in the blood. Aspirin is not recommended in children with fever because of the risk of developing Reye syndrome.

Sweats and Hot Flashes

Sweat is made by sweat glands in the skin. Sweating helps to keep the body cool and can occur with disease or fever, when in a warm environment, exercising, or as part of hot flashes experienced with menopause. Most breast cancer and prostate cancer patients report having moderate-to-severe hot flashes. Distressing hot flashes seem to be less frequent and gradually decrease with time in most postmenopausal women who do not have breast cancer. Hot flashes occur in most men with prostate cancer who have had surgery to remove the testicles or who receive drugs to stop the testicles from making testosterone.

Sweats in the cancer patient may be associated with the tumor, cancer treatment, or other medical conditions that are not related to the cancer. Sweats are a typical symptom of certain types of tumors such as Hodgkin lymphoma, pheochromocytoma, or tumors involving the nervous system and endocrine system. Sweats may also be caused by:

• Fever.

• Female menopause (natural menopause, surgical removal of the ovaries, or damage to ovaries from chemotherapy, radiation, or hormone therapy).

• Male menopause (surgical removal of the testicles or hormone therapy).

• Drugs such as tamoxifen, aromatase inhibitors, opioids, antidepressants, and steroids.

• Problems in the hypothalamus in the brain.

• Sweating disorders.

Treatment of sweats caused by fever is directed at the underlying cause of the fever. (Refer to the fever Treatment ³ section for more information.) Sweats caused by a tumor are usually controlled by treatment of the tumor.

Hot flashes associated with natural or treatment-related menopause can be effectively controlled with estrogen replacement therapy. Many women are not able to take estrogen replacement (for example, women with breast cancer). Hormone replacement therapy that combines estrogen with progestin may increase the risk of breast cancer or breast cancer recurrence.

Studies of non-estrogen drugs to treat hot flashes in women with a history of breast cancer have reported that many of them are not as effective as estrogen replacement or have unwanted side effects. The most effective of these include megestrol (a drug similar to progesterone), certain antidepressants, anticonvulsants, and clonidine (a drug used to treat high blood pressure). Some antidepressants may change how other drugs, such as tamoxifen, work in the body. Different patients may respond in different ways to certain drugs and some side effects can be serious. It is important that the members of a patient's health care team know about all medicines and herbals the patient is taking.

Drugs that may relieve nighttime hot flashes or night sweats and improve sleep at the same time are being studied in clinical trials.

Studies of vitamin E for the relief of hot flashes show that it is only slightly better than a placebo (pill that has no effect). Most studies of soy and black cohosh show they are no better than a placebo in reducing hot flashes. Soy contains estrogen-like substances; the effect of soy on the risk of breast cancer growth or recurrence is not clear. Ground flaxseed continues to be studied for its potential to relieve hot flashes.

Claims are made about several other plant-based and natural products as remedies for hot flashes. Since little is known about how they work or whether they affect the risk of breast cancer, women should be cautious about using these products, including dong quai, milk thistle, red clover, licorice root extract, and chaste tree berry.

Treatment of hot flashes in men who have been treated for prostate cancer may include estrogens, progesterone, antidepressants, and anticonvulsants. Certain hormones (such as estrogen) can make some cancers grow. The effect of hormone use on the growth of prostate cancer is being studied.

Side effects of antidepressants used to treat hot flashes over a short period of time are minor, including nausea, drowsiness, dry mouth, and changes in appetite. Side effects of anticonvulsants used to treat hot flashes include drowsiness, dizziness, and trouble concentrating. Side effects of clonidine include dry mouth, drowsiness, constipation, and insomnia.

If one medication does not improve symptoms, switching to another medication may be helpful.

Comfort measures are used for general treatment of cancer-related sweats. Since body temperature goes up before a hot flash, the following ways may control body temperature and help manage symptoms:

• Wear loose-fitting clothes.
• Use fans and open windows to keep air moving.
• Learn relaxation training and slow, deep breathing.
• Use self- hypnosis.

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