St. Jude Study Shows Long-term Anticonvulsant Therapy Hinders Positive Effects of Chemotherapy

St. Jude Children's Research Hospital (ALSAC)
Friday, 21 July 2000

Antiseizure medicine given to patients with acute lymphoblastic leukemia counteracts cancer-fighting agents

(Memphis, Tennessee, July 21, 2000)— Investigators at St. Jude Children's Research Hospitalâ discovered that some anti-seizure medicines given to children with acute lymphoblastic leukemia (ALL), the most common form of childhood cancer, can decrease the chance of cure of leukemia.

In a study published in the July 21 issue of the journal The Lancet, St. Jude researchers determined that children who received the antiseizure medicines phenytoin, phenobarbital and carbamazepine, which potently increase the amount of drug-metabolizing enzymes in the liver, have lower chances of event-free survival than those who did not receive such medicines. The liver enzymes are responsible for clearing many clinically-used medications from the body, so that the use of these antiseizure medicines may be comparable to lowering the doses of the antileukemic chemotherapy.

According to lead investigator Mary Relling, Pharm.D., a clinical pharmacist at St. Jude, the scientific team studied 716 patients with ALL from 1984 to 1993. Of those patients, about 5.6 percent took these anticonvulsants to treat or prevent seizures.

"There are about 20 to 30 primary drug-metabolizing enzymes that help clear medications from our bodies," Relling said. "Medications will be either eliminated unchanged by the kidney, or will be broken down into more water-soluble forms and eliminated in the urine. These particular anticonvulsant medicines dramatically increase the amount of many different kinds of metabolizing enzymes in the liver. Therefore, almost any medication that's subject to liver metabolism is going to be eliminated from the body more quickly. So, if we can avoid using these anticonvulsant medications, we can have better outcomes in the treatment of childhood ALL."

Two possible ways to avoid these drug interactions include minimizing the amount of time patients take anticonvulsants or, if a patient requires chronic anticonvulsants at the same time as their chemotherapy, using newer anticonvulsant medications that do not have the propensity to increase these enzymes in the liver.

"To keep improving outcomes in childhood leukemia, it is helpful to identify treatment-related prognostic factors like this because they can be more easily altered [as opposed to genetic factors] to overcome the negative impact," Relling said. Other St. Jude investigators involved in the study included Ching-Hon Pui, M.D., John Sandlund, M.D., Gaston Rivera, M.D., Michael Hancock, Ph.D., James Boyett, Ph.D., Erin Schuetz, Ph.D., and William Evans, Pharm.D.

St. Jude was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC) . All St. Jude Children's Research Hospital patients are treated regardless of their ability to pay.

ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org