PURPOSE: To study the efficacy and tolerability of valproic acid (VPA) and 
radiation, followed by VPA and bevacizumab in children with newly diagnosed 
diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG).
METHODS: Children 3 to 21 years of age received radiation therapy and VPA at 
15 mg/kg/day and dose adjusted to maintain a trough range of 85 to 115 μg/mL. 
VPA was continued post-radiation, and bevacizumab was started at 10 mg/kg 
intravenously biweekly, four weeks after completing radiation therapy.
RESULTS: From September 2009 through August 2015, 20 DIPG and 18 HGG patients 
were enrolled (NCT00879437). During radiation and VPA, grade 3 or higher 
toxicities requiring discontinuation or modification of VPA dosing included 
grade 3 thrombocytopenia (1), grade 3 weight gain (1), and grade 3 pancreatitis 
(1). During VPA and bevacizumab, the most common grade 3 or higher toxicities 
were grade 3 neutropenia (3), grade 3 thrombocytopenia (3), grade 3 fatigue (3), 
and grade 3 hypertension (4). Two patients discontinued protocol therapy prior 
to disease progression (one grade 4 thrombosis and one grade 1 intratumoral 
hemorrhage). Median event-free survival (EFS) and overall survival (OS) for DIPG 
were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS 
was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) 
months, and estimated one-year EFS was 24% (7%-45%). Four patients with 
glioblastoma and mismatch-repair deficiency syndrome had EFS of 28.5, 16.7, 
10.4, and 9 months.
CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but 
did not appear to improve EFS or OS in children with DIPG or HGG.