Hydroxyurea

Definition

Hydroxyurea, also known by its trade name Hydrea, is an antineoplastic agent, meaning it is used to treat cancer. It is taken orally.

Purpose

Hydroxyurea is used to treat the following conditions:

• Melanoma
• Chronic myelocytic leukemia that is resistant to other therapies
• Ovarian cancer that is recurrent, metastatic or inoperable.
• Squamous cell carcinoma of the head and neck, excluding the lip. (In this case, it is treated with radiation therapy.)
• Sickle cell anemia
• Other: Hydroxyurea has shown promise in the management of thrombocytosis, a condition in which platelet levels are abnormally high

Description

Hydroxyurea belongs to antimetabolites, a group of compounds that interfere with the production of nucleic acids. Hydroxyurea exerts its anticancer activity by inhibiting ribonucleotide reductase, an enzyme required for DNA synthesis. When used in conjunction with radiation therapy, the effectiveness of hydroxyurea increases because it also inhibits the ability of cells damaged by radiation to repair themselves.

Recommended dosage

Hydroxyurea dosages are calculated based on a person's weight as milligrams per kilogram (mg/kg). Doctors will usually use whichever value is lowest—the patient's actual weight or the patient's ideal weight—to calculate dosages. The drug is not given if white blood cell levels drop below 2500 mm³, or if red blood cell levels drop below100,000 mm³. Usually, bone marrow recovery is rapid, and few doses are missed. Hydroxyurea is usually given for six weeks before its effectiveness can be adequately evaluated.

Hydroxyurea is administered in a capsule form, each containing 500 mg of the drug. If a patient is unable to swallow the capsule, its contents can be dissolved in a glass of water and swallowed immediately. The drug will not completely dissolve in water. Dosages have not been established for children in part because the cancers for which hydroxyurea is useful do not normally occur in that age group.

In the treatment of solid tumors, such as ovarian cancers, patients are usually given 80 mg/kg once every three days. Alternatively, a dose of 20-30 mg/kg may be given every day.

In head and neck cancers also treated with radiation, 80 mg/kg of hydroxyurea is given once every three days. The drug should be started a week before radiation therapy begins, and should continue for some time after radiation therapy.

When it is used to treat resistant chronic myelocytic leukemia, hydroxyurea is given in the dosage of 20-30 mg/kg once a day.

In thrombocytosis, doses of 15-30 mg/kg taken once a day are usually effective. Platelet levels return to a normal level within two to six weeks of therapy. In more severe cases, doses of 1.5-3.0 grams per day have been given with plateletpheresis, a procedure that removes platelets from the blood.

Precautions

This drug should not be administered to a person who has had a previous allergic reaction to it. Liver and kidney function should be evaluated prior to, and during, treatment. The drug may interfere with certain lab tests. For example, creatinine levels may be elevated. Patients taking hydroxyurea should stay well-hydrated, drinking up to 12 glasses per day of water or other fluids.

Hydroxyurea is potentially mutagenic, meaning that it causes mutations in DNA. Patients taking the drug should discuss the potential effects on their future conception plans. Hydroxyurea should not be administered to pregnant women, and women taking the drug should use birth control methods to prevent pregnancy. Hydroxyurea is excreted in breast milk; therefore, women taking the drug should not breast-feed.

Side effects

Hydroxyurea and radiation therapy each cause adverse side effects. When they are used together, the incidence and severity of side effects may increase.

Bone marrow suppression is the major side effect of hyroxyurea therapy, and may develop within two days of the first dose. Blood tests are performed routinely to monitor for changes. Usually, leukopenia (decreased white blood cells) develops first. Reduced red blood cells and platelets can also occur, but generally not as frequently. If anemia develops, it should be corrected with whole blood transfusions. Hydroxyurea causes red blood cell abnormalities that are not severe and that do not reduce the red blood cell survival time.

Gastrointestinal symptoms are not as common as myelosuppression and are usually mild. These symptoms may include nausea, vomiting, diarrhea, and constipation. Usually, medications can control nausea and vomiting. Mucositis, a painful swelling of the mucous membranes, may also develop, especially if the patient is undergoing radiation treatment to the head and neck. Mucositis can be managed with medicated mouthwashes, good oral hygiene, and hydration to keep the mouth moist.

Headache and dizziness may occur. With long-term use, skin changes, such as hyperpigmentation of the skin and nails, have also been reported.

Interactions

Patients at risk for bone marrow suppression should inform their doctor about all medications they are taking, both prescription and non-prescription. Many over-the-counter medications contain aspirin, which acts as a blood-thinner, increasing the potential for bleeding. Patients with reduced platelets should not take aspirin.

Tamara Brown, R.N.

Mucositis

—A painful inflammation of the mucous membranes.

Mutagen

—An agent capable of causing DNA changes.

Myelosuppression

—Diminished bone marrow activity resulting in decreased red blood cells, white blood cells, and platelets.

Plateletpheresis

—A procedure in which platelets are removed from whole blood.