Choice of antiepileptic drug for brain tumor patients may affect survival

New research suggests brain tumor patients who take the antiepileptic drug valproic acid on top of standard treatment may live a few months longer than people who take other kinds of epilepsy medications to control seizures. The research is published in the 31 August 2011 online issue of Neurology®, the medical journal of the American Academy of Neurology.

“While our research is limited and further studies are needed to confirm our findings, these results suggest that the choice of antiepileptic medications in brain tumor patients should be carefully considered as it may give people a few more months with their loved ones,” said study author Michael Weller, MD, with the University Hospital Zurich in Switzerland and a member of the American Academy of Neurology.

Seizures occur in up to half of all people with glioblastomas, a common and highly malignant type of brain tumor. For those patients with seizures, treatment with one of several antiepileptic drugs is highly recommended. After surgery, standard treatment for patients with newly diagnosed brain tumors is radiation therapy and the drug temozolomide.

For this study, researchers analyzed the use of antiepileptic drugs by 573 brain tumor patients who had been enrolled in the EORTC 26981-22981/National Cancer Institute of Canada CE.3 clinical trial involving radiation therapy with and without temozolomide.  When treatment started, 175 were not taking an antiepileptic drug, 252 were taking an enzyme-inducing antiepileptic drug, and 97 were taking a non-enzyme-inducing antiepileptic drug such as valproic acid. Thirty eight received both an enzyme-inducing antiepileptic drug and valproic acid. The status of antiepileptic drug administration was unknown in 11.

While the overall survival of patients taking an antiepileptic drug was similar to those not taking any antiepileptic drug, the study found that the 49 patients taking valproic acid appeared to have an increased survival benefit of three months (median survival 17.35 months, 95% Confidence Interval (CI): 14.59, 22.87) from treatment with radiation therapy and temozolomide compared to patients receiving enzyme-inducing antiepileptic drugs (median survival 14.42 months, 95% CI: 12.35, 16.30) or patients not taking an antiepileptic drug (median survival 13.96 months, 95% CI: 12.12, 18.07).

While survival did increase, people taking valproic acid in addition to radiation therapy and temozolomide were more likely than the other groups to experience a decrease in blood platelets and white blood cells which can increase the risk of bleeding and infection.

Taking valproic acid did not benefit survival in the group that received radiation therapy alone without temozolomide.  Dr. Weller said further research is needed to determine why valproic acid may help patients who are receiving radiation therapy and temozolomide live longer.

The clinical trial was partially supported by the National Cancer Institute in the United States and a grant from the Swiss Cancer League (Schweizerische Krebsliga) to the EORTC Charitable Trust.

Founded in 1962, European Organisation for Research and Treatment of Cancer (EORTC) is a nonprofit international cancer research organization under Belgian law. The EORTC has the mission to develop, conduct, coordinate and stimulate translational and clinical research in Europe to improve the management of cancer and related problems by increasing survival but also patient quality of life. The EORTC is both multinational and multidisciplinary, and the EORTC Network comprises over 300 hospitals and cancer centers in over 30 countries which include some 2,500 collaborators from all disciplines involved in cancer treatment and research.

John Bean
Thierry Gorlia

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