Effect of valproic acid on survival in glioblastoma: A prospective single-arm study

Abstract

Background: Retrospective evidence suggests that valproic acid (VPA), an antiepileptic drug, is associated with improved outcomes in glioblastoma. The exact mechanism of interaction of VPA with radiation and temozolomide (TMZ) is still unclear. Laboratory studies show that VPA can enhance tumor cell kill while at the same time protect the normal neural tissue. The aim of this study was to prospectively evaluate the benefit of VPA on outcomes in glioblastoma. Materials and Methods: In this single-arm prospective study, patients of glioblastoma were started on seizure prophylaxis with VPA (15–20 mg/kg/day) following maximal safe resection. All patients were treated with chemoradiation to a dose of 60 Gy in 30 fractions with concurrent TMZ followed by adjuvant TMZ for 6 cycles. VPA was continued during adjuvant treatment and follow-up. Survival analysis was done using Kaplan–Meier analysis. Results: Twenty patients were enrolled in the study. Median age was 47 years. M:F ratio was 3:1. Treatment was well tolerated with no grade 3/4 adverse events. 8/20 patients experience seizure episodes during treatment and/or follow-up which needed additional antiepileptic drugs for control. Median progression-free survival (PFS) and overall survival (OS) were 10 months and 16 months, respectively. Younger patients (age ≤45 years) showed a significantly better OS (25 months) versus older patients (8 months) (P = 0.002). Conclusions: Incidence of seizures on VPA prophylaxis was 40%. Median PFS and OS were comparable to historical controls. There was no significant treatment-related toxicity. The results need validation in larger prospective randomized studies.

Keywords

• Chemoradiation
• glioblastoma
• survival
• valproic acid