National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
January 24, 2012 • Volume 9 / Number 2

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FDA Update

Glucarpidase Approved to Lower Toxic Chemotherapy Levels in the Blood

Last week, the Food and Drug Administration (FDA) approved glucarpidase (Voraxaze) to treat patients with toxic levels of the chemotherapy methotrexate (Abitrexate) in their blood.

The kidneys usually eliminate methotrexate from the body, but patients receiving high doses of methotrexate can develop kidney failure. Glucarpidase is an enzyme that rapidly breaks down methotrexate into a nontoxic form that can be eliminated from the body more rapidly.

“Prolonged exposure to high levels of methotrexate can result in kidney and liver damage, severe mouth sores, damage to the lining of the intestine, skin rashes, and death due to low blood counts,” explained Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a news release.

Glucarpidase is designated an orphan drug, a designation given to therapies for diseases or conditions that affect fewer than 200,000 people in the United States.

In a clinical study of 22 patients, treatment with intravenous glucarpidase was effective in 10 patients—that is, patients’ methotrexate levels fell below a critical level within 15 minutes and stayed below that level for 8 days. (Methotrexate levels were analyzed at NCI using a sensitive and specific test.) Although not all patients experienced this result, glucarpidase eliminated 95 percent of the methotrexate in all patients.

A separate clinical study evaluated the safety of glucarpidase in 290 patients experiencing problems clearing methotrexate from their blood. The most common side effects observed in the study were low blood pressure, headache, nausea, vomiting, flushing, and abnormal skin sensation (paresthesia).

Most of these patients were enrolled in a compassionate-use trial run by NCI’s Cancer Therapy Evaluation Program. The trial showed that glucarpidase was well tolerated and resulted in a rapid and profound decrease in methotrexate concentrations in the blood.

New Warnings Added for Lymphoma Drug

The Food and Drug Administration (FDA) has added a boxed warning for the lymphoma drug brentuximab vedotin (Adcetris) highlighting the risk of progressive multifocal leukoencephalopathy (PML), a rare but serious viral infection of the brain that can result in death. The agency has also added a new contraindication warning against the use of brentuximab vedotin with the cancer drug bleomycin due to increased risk of lung toxicity, characterized by cough or shortness of breath.

The FDA approved brentuximab vedotin for patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma in August 2011. The treatment combines a drug with an antibody that directs the drug to a target on lymphoma cells. At the time of the drug’s approval, one case of PML was described in the drug’s safety information. In a drug safety communication issued January 13, the FDA alerted the public to two additional cases of PML.

The signs and symptoms of PML can develop over several weeks or months. They may include changes in mood or in usual behavior; confusion; thinking problems; loss of memory; changes in vision, speech, or walking; and decreased strength or weakness on one side of the body. Patients who develop any signs or symptoms of PML should notify their health care professional immediately. Brentuximab vedotin treatment should be suspended if PML is suspected and discontinued if PML is confirmed.

Patients and health care professionals should report serious side effects from the use of brentuximab vedotin, including confirmed cases of PML, to the FDA MedWatch program online or by calling 1-800-332-1088.

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