Valproic acid use during radiation therapy for glioblastoma associated with improved survival Journal Article


Authors: Barker, C. A.; Bishop, A. J.; Chang, M.; Beal, K.; Chan, T. A.
Article Title: Valproic acid use during radiation therapy for glioblastoma associated with improved survival
Abstract: 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). 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. 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. 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. Copyright © 2013 Elsevier Inc. All rights reserved.
Keywords: survival; adolescent; adult; treatment outcome; aged; middle aged; survival analysis; retrospective studies; young adult; histone deacetylase inhibitor; mortality; multimodality cancer therapy; combined modality therapy; temozolomide; brain tumor; methodology; brain neoplasms; dacarbazine; alkylating agent; retrospective study; glioblastoma; antineoplastic agents, alkylating; drug derivative; histone deacetylase inhibitors; multivariate analysis; seizure; anticonvulsive agent; anticonvulsants; valproic acid; seizures
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 86
Issue: 3
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2013-07-01
Start Page: 504
End Page: 509
Language: English
PUBMED: 23523186
PROVIDER: scopus
PMCID: PMC4667941
DOI: 10.1016/j.ijrobp.2013.02.012
DOI/URL:
Notes: - "Export Date: 1 August 2013" - "Source: Scopus"
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  1. Timothy Chan
    317 Chan
  2. Kathryn Beal
    221 Beal
  3. Christopher Barker
    218 Barker
  4. Andrew Justin Bishop
    5 Bishop
  5. Maria Chang
    10 Chang