BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive type of primary 
brain tumor. It is a rapidly progressive, highly recurrent, fatal intracranial 
neoplasm, and the demand for novel treatment is urgent. Valproic acid (VPA) is a 
potential anticancer agent that belongs to a class of histone deacetylase (HDAC) 
inhibitors, targeting the epigenetic control of gene functions in cancer cells. 
This drug has been administered for the prevention or treatment of seizure 
disorder in GBM patients; therefore, a retrospective analysis may further our 
understanding of the effect of VPA on GBM patients.
MATERIALS AND METHODS: A retrospective analysis of 102 patients with GBM was 
conducted to study the effects of VPA on disease outcome. Tumor samples from 
seven patients receiving VPA treatment between the first and second operations 
were obtained in order to verify the HDAC inhibitory activity of VPA in these 
patients.
RESULTS: In univariate analysis, administration of VPA within 2 weeks of initial 
diagnosis seemed to confer a survival benefit. However, stratified analysis 
according to chemotherapy showed that VPA did not have significant impact on the 
GBM patients' overall survival. Analysis of tissue samples from these patients 
revealed that a small subset of patients had increased histone acetylation after 
VPA treatment.
CONCLUSION: VPA treatment, when administered according to a protocol targeting 
seizure control, may result in HDAC inhibition in a small subset of patients, 
but does not significantly affect overall patient survival. Early administration 
of VPA as an adjunct to temozolomide chemotherapy may have its merits, but the 
optimal dosing schedule and target serum level require further investigation.