Evidence map›Paper›PMID 26786929›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2016

Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma.

Caroline Happold, Thierry Gorlia, Olivier Chinot, Mark R Gilbert, L Burt Nabors, Wolfgang Wick, Stephanie L Pugh, Monika Hegi, Timothy Cloughesy, Patrick Roth and 5 more

4 registry-linked trialsOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 117 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 4 pooled it
13.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00689221 phase3completednot on this map

Cilengitide for Subjects With Newly Diagnosed Glioblastoma and Methylated MGMT Gene Promoter - A Multicenter, Open-label, Controlled Phase III Study, Testing Cilengitide in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy) Versus Standard Treatment Alone (CENTRIC)

TypeinterventionalSponsorEMD SeronoRan2008 to 2013Enrolled545ConditionsGlioblastomaArmsCilengitide, Temozolomide, Radiotherapy
NCT00813943 phase2completednot on this map

Cilengitide in Subjects With Newly Diagnosed Glioblastoma and Unmethylated MGMT Gene Promoter - a Multicenter, Open-label Phase II Study, Investigating Two Cilengitide Regimens in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy). [The CORE Study]

TypeinterventionalSponsorEMD SeronoRan2009 to 2013Enrolled265ConditionsGlioblastomaArmsCilengitide (2-times weekly), cilengitide (5-times weekly), Temozolomide, Radiotherapy
NCT00884741 phase3completednot on this map

Phase III Double-blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2009 to 2013Enrolled637ConditionsGlioblastoma, Gliosarcoma, Supratentorial GlioblastomaArms3-Dimensional Conformal Radiation Therapy, Bevacizumab, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Placebo
NCT00943826 phase3completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Bevacizumab, Temozolomide and Radiotherapy, Followed by Bevacizumab and Temozolomide Versus Placebo, Temozolomide and Radiotherapy Followed by Placebo and Temozolomide in Patients With Newly Diagnosed Glioblastoma

TypeinterventionalSponsorHoffmann-La RocheRan2009 to 2015Enrolled921ConditionsGlioblastomaArmsBevacizumab, Temozolomide, Radiation therapy, Placebo
3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 4 syntheses or guidelines pooled it, 209 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Management of epilepsy in brain tumors.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019
    Guideline
  5. Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Article
  11. Article
  12. Obstacles and Trials in Treating Primary Brain Tumors.International journal of molecular sciences · 2026
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Caroline HappoldCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Thierry GorliaCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Olivier ChinotCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Mark R GilbertCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
L Burt NaborsCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Wolfgang WickCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Stephanie L PughCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Monika HegiCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Timothy CloughesyCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Patrick RothCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
David A ReardonCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
James R PerryCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Minesh P MehtaCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Roger StuppCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD.
Michael WellerCaroline Happold, Patrick Roth, Roger Stupp, and Michael Weller, University Hospital Zurich; Monika Hegi, University Hospital Lausanne, Switzerland; Thierry Gorlia, EORTC Data Centre, Brussels, Belgium; Olivier Chinot, Aix-Marseille University, Marseille, France; Mark R. Gilbert, The University of Texas MD Anderson Cancer Center, Houston, TX; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Wolfgang Wick, University of Heidelberg & German Cancer Research Center, Heidelberg, Germany; Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Timothy Cloughesy, UCLA Neuro-Oncology Program, Los Angeles, CA; David A. Reardon, Dana-Farber Cancer Institute, Boston, MA; James R. Perry, University of Toronto, Toronto, Ontario, Canada; and Minesh P. Mehta, University of Maryland, Baltimore, MD. michael.weller@usz.ch.
German Cancer Research Center · DE

Funding

NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
RTOG Foreign AccrualU10CA021661 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI CURRAN, WALTER J. · 1985 to 2013
$150.3M
Statistics CoreU10CA180822 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mei-Yin C Polley · 2014 to 2026
$146.4M
NCI NIH HHS U10 CA021661NCI NIH HHS U10 CA180822NCI NIH HHS U10 CA180868
6 · The paper itself

Abstract

purposeSymptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. PATIENTS AND

methodsTo confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV).

resultsVPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use.

conclusionThe results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.

Indexed as

AdolescentAdultAgedAnticonvulsantsAntineoplastic Agents, AlkylatingBrain NeoplasmsChemoradiotherapyClinical Trials as TopicDacarbazineEpilepsyFemaleGlioblastomaHumansLevetiracetamMaleMiddle AgedAnticonvulsantsAntineoplastic Agents, AlkylatingDacarbazineLevetiracetamPiracetamTemozolomideValproic Acid

Identifiers

PMID26786929
PMCPMC5070573
OpenAlexW2256711934

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.