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A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high‐grade glioma
Author(s) -
Su Jack MengFen,
Murray Jeffrey C.,
McNallKnapp Rene Y.,
Bowers Daniel C.,
Shah Shafqat,
Adesina Adekunle M.,
Paulino Arnold C.,
Jo Eunji,
Mo Qianxing,
Baxter Patricia A.,
Blaney Susan M.
Publication year - 2020
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28283
Subject(s) - medicine , bevacizumab , tolerability , glioma , neutropenia , gastroenterology , valproic acid , discontinuation , radiation therapy , phases of clinical research , surgery , oncology , chemotherapy , epilepsy , adverse effect , cancer research , psychiatry
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.