Patients undergoing chemotherapy and radiotherapy for malignant glioblastoma appear to have better overall survival if they also receive the antiseizure medication valproic acid (VPA), according to a new study.

Researchers at University Hospital Zurich (UHZ; Switzerland), University Hospital Tübingen (Germany), and other institutions conducted a retrospective analysis of data from a pivotal trial of temozolomide and radiation (TMZ/RT) for glioblastoma to see if overall survival or progression-free survival (PFS) were influenced by antiepileptic drug (AED) use. The study included 573 patients with glioblastoma who were treated with radiotherapy alone or with TMZ between 2000 and 2002; 68% received an AED, and of those, 28% were prescribed a nonenzyme inducing agent, which most often was VPA. The researchers measured drug efficacy after adjustment for patient age, degree of tumor resection, use of corticosteroids, and scores on Mini-Mental State Examination (MMSE).

The results showed that when treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED), and 135 (23.4%) were taking any non-EIAED. Patients receiving VPA only had more grade 3/4 thrombopenia and leukopenia than patients without an AED, or patients taking an EIAED only. The overall survival of patients who were receiving an AED at baseline versus not receiving any AED was similar. Patients receiving VPA alone appeared to derive more survival benefit from TMZ/RT than patients receiving an EIAED only, or patients not receiving any AED. The study was published in the September 20, 2011, issue of Neurology.

“Despite the limitations of this retrospective analysis, these results suggest that the choice of an antiepileptic drug in patients with brain tumors should be carefully considered because it may affect survival,” concluded lead author Michael Weller, MD, of the UHZ department of neurology, and colleagues.

Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression; it is also used to treat migraine headaches and schizophrenia. The researchers suggest that the improved response to radiotherapy and chemotherapy in patients treated with valproic acid may result from the drug's ability to inhibit histone deacetylase, leading to radiochemotherapy sensitization.

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