BACKGROUND: Chemotherapy has limited effects in the treatment of high-grade 
gliomas (HGGs). Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, may 
sensitize HGGs to radiochemotherapy. As the drug has been given frequently as an 
antiepileptic drug, a retrospective analysis was conducted to ensure relevant 
information was not missed before a prospective study was launched.
MATERIALS AND METHODS: An analysis of 66 pediatric patients (range, 1-19 years 
of age) with glioblastoma multiforme (GBM) (n=40) or anaplastic astrocytoma (AA) 
(n=26) was retrospectively conducted for predictors of survival and response and 
for effects of VPA on outcome or toxicity.
RESULTS: The overall survival (OS) was better for AA (p=0.0114) and complete 
resection (p<0.00005) and event-free survival (EFS) was better for complete 
resection (p=0.0049). Nine patients received VPA (for seizure) plus further 
oncological treatment. The most severe adverse effect was a pulmonary embolism 
(n=1); no other severe side-effects were noted. The response to nonsurgical 
treatment after 8 weeks was: complete response (CR): 0, partial response (PR): 
3, stable disease (SD): 4, progressive disease (PD): 2. Some of the patients 
with SD responded later resulting in best response: CR:0, PR:5, SD:2, PD:2.
CONCLUSION: Treatment with VPA plus radiochemotherapy is well tolerated with an 
encouraging response rate.