PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone 
deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage 
seizures, and it can modulate the biologic effects of radiation therapy (RT). We 
investigated whether VA use during RT for GB was associated with overall 
survival (OS).
METHODS AND MATERIALS: Medical records of 544 adults with GB were 
retrospectively reviewed. Analyses were performed to determine the association 
of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) 
class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT 
with OS.
RESULTS: Seizures before the end of RT were noted in 217 (40%) patients, and 403 
(74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in 
patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). 
Among patients taking an AED during RT, OS was associated with VA (P=.047; 
hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA 
class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA 
was associated with OS. Median OS of patients receiving VA and TMZ during RT was 
23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the 
analysis was restricted to patients who received concurrent TMZ, VA use was 
marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), 
independently of RTOG RPA class and seizure history.
CONCLUSIONS: VA use during RT for GB was associated with improved OS, 
independently of RTOG RPA, seizure history, and concurrent TMZ use. Further 
studies of treatment that combines HDAC inhibitors and RT are warranted.