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.

Abstract

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.

• Authors: Jack Meng-Fen Su, Jeffrey C Murray, Rene Y McNall-Knapp, Daniel C Bowers, Shafqat Shah, Adekunle M Adesina, Arnold C Paulino, Eunji Jo, Qianxing Mo, Patricia A Baxter, Susan M Blaney
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 67 Issue 6 Pg. e28283 (06 2020) ISSN: 1545-5017 [Electronic] United States
• PMID: 32285998 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Bevacizumab
• Valproic Acid

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab (administration & dosage)
• Brain Stem Neoplasms (pathology, therapy)
• Chemoradiotherapy (mortality)
• Child
• Child, Preschool
• Diffuse Intrinsic Pontine Glioma (pathology, therapy)
• Female
• Follow-Up Studies
• Humans
• Male
• Prognosis
• Survival Rate
• Valproic Acid (administration & dosage)
• Young Adult