Glucarpidase Approved to Lower Toxic Chemotherapy Levels in the Blood ► NCI Cancer Bulletin for January 24, 2012 - National Cancer Institute

NCI Cancer Bulletin for January 24, 2012 - National Cancer Institute

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.