Carmustine is an antineoplastic drug, meaning that it inhibits the growth of cancer. It does this by disrupting DNA and synthesis, which leads to cell death. Carmustine is often referred to as BCNU, and along with other chemically similar drugs (lomustine, semustine, and streptozocin) is classified as a nitrosourea. Brand names for carmustine in the U.S. include BiCNU and Gliadel Wafers.
Purpose
Because it readily crosses the blood-brain barrier, carmustine is used to treat several types of brain tumors, including astrocytoma, ependymoma, glioblastoma, brainstem glioma, medulloblastoma. It is usually given intravenously, but it is also available as a wafer that is implanted in the brain during surgery. Carmustine is also used in the treatment of multiple myeloma and melanoma, usually in combination with other agents. It is also used in high does for patients undergoing bone marrow or stem cell transplants. Patients with non-Hodgkin's or Hodgkin's lymphoma whose disease has either relapsed or not responded to initial therapy, may be treated with carmustine used in combination with other drugs.
Description
Carmustine was approved for use by the U.S. Food and Drug Administration (FDA) in 1977. Carmustine comes in vial, in a powder form, and is reconstituted with sterile water according to the manufacturer's instructions. It may be used as a single agent, meaning it is administered alone; or it may be used with other drugs. It is further diluted in a larger volume of fluid and given slowly into a vein over a one-to two-hour period. Faster administration may cause a burning sensation in the vein, as well as facial flushing. The wafer is implanted surgically.
Carmustine is excreted by the kidneys during urination, and the lungs during expiration. Studies have shown that within four days, up to 70% of the drug is excreted in the urine, while an additional 10% is excreted in exhaled carbon dioxide. No one is certain what happens to the remaining 20% of the drug.
Recommended dosage
Because carmustine can have delayed toxic effects on the bone marrow, doses should be given at least four to six weeks apart. If carmustine is given in conjunction with other drugs that also suppress the bone marrow, dosages may be reduced. Blood tests are performed frequently during and after treatment, and their results may require dosage adjustments. Currently, there is no known remedy for a carmustine overdose.
Chemotherapy dosages are based on a person's body surface area (BSA), which is calculated in square meters using height and weight measurements. Drug dosages are ordered in milligrams per square meter (mg/m2). Carmustine doses vary, but common doses include 75-250 mg/m2 every four to six weeks, and 80 mg/m2 daily for three days every six weeks. Higher doses are used for patients undergoing bone marrow or stem cell transplants. The specific dose should be verified for each patient. Continued doses after the first course of carmustine depend on the patient's response and on toxi-city. Sometimes doses are adjusted because of toxicity or low blood counts.
Precautions
Carmustine may be damaging to an unborn fetus. Women of child-bearing potential should take measures to prevent pregnancy and women receiving carmustine should not breast-feed.
Side effects
Carmustine should be used after careful consideration of the risks and benefits involved, as there can be serious adverse side effects.
Myelosuppression
Effects on the bone marrow can lead to reduced numbers of platelets and white blood cells, which can
have potentially life-threatening results, including bleeding and infection. These effects are first seen from four to six weeks after treatment is started, are cumulative, and are related to the amount of the drug given. A patient taking carmustine who develops a fever or notices an increased tendency to bleed or bruise may have dangerously low blood counts, and should be evaluated by a physician.
Pulmonary damage
Patients taking carmustine are at risk for damage to the lungs marked by pulmonary fibrosis. The main symptom of pulmonary fibrosis is shortness of breath. Pulmonary fibrosis can lead to heart failure. It is most likely to develop in patients with total cumulative doses greater than 1400 mg/m2, although lower doses may also cause damage.
Individuals with underlying lung disease, such as chronic obstructive pulmonary disease, may be more likely to develop carmustine-associated pulmonary injury. Prior to initiating treatment with carmustine, a doctor will usually evaluate how well the lungs function by performing pulmonary function tests (PFTs). Patients are more likely to develop lung damage if portions of these tests are abnormal. PFTs may be repeated during treatment to monitor for adverse effects of carmustine. If carmustine is used in conjunction with other drugs that have toxic effects on pulmonary function, there may be a greater risk of lung damage.
Nausea and vomiting
Like many antineoplastic drugs, carmustine can cause nausea and vomiting. Before carmustine is administered, medications called antiemetics should be given to prevent or minimize nausea. Patients who experience severe nausea, or nausea that is uncontrolled with antiemetics, should notify their doctor.
Organ damage
Carmustine may cause damage to the kidneys. With careful monitoring and frequent blood tests, this damage can be prevented or reversed. Kidney damage is more likely to occur in individuals who have received prolonged therapy with large cumulative doses. Blood tests to evaluate renal function should be performed routinely. Carmustine may be discontinued or reduced depending on these results.
Secondary malignancies
Although carmustine is used to treat cancer, it may also cause secondary malignancies when used long-term.
Carmustine wafers
Intracranial implantation of carmustine wafers has been associated with abnormal wound healing after surgery, brain edema or accumulation of fluid, infection, and the formation of cysts near the site of implantation.
Interactions
Patients should tell their doctor about medications they are taking in addition to their cancer treatment, as these medications may interact with carmustine. For example, cimetidine, a drug used to treat heartburn and ulcers, may increase the toxic effects of carmustine on the bone marrow. Carmustine, on the other hand, may decrease blood levels of phenytoin, a drug used in the treatment of patients with seizures. If blood levels are too low, seizures may not be prevented.
Patients undergoing treatment for cancer with carmustine should talk to their doctor prior to taking any vaccines. Live vaccines, in particular, can increase the likelihood of complications.
Aspirin and ibuprofen, which are found in many over-the-counter products, should be avoided. These drugs can increase the potential for bleeding in people who may already have decreased platelet counts due to carmustine therapy.
Tamara Brown, R.N.
Antiemetic
—A drug that prevents or alleviates nausea and vomiting.
Body surface area
—A measurement based on height and weight that is expressed in square meters. It is used to determine chemotherapy dosages.
Myelosuppression
—Suppression of bone marrow function that results in decreased platelets, red blood cells, and white blood cells.
