Trial reportInternational journal of radiation oncology, biology, physics2015
A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma.
Trial report in International journal of radiation oncology, biology, physics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02758366 (An Open-label, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Doxorubicin in Combination With Radiotherapy, Temozolomide and Valproic Acid in Patients With Glioblastoma Multiforme), which is not on this map. Cited by 128 papers, 4 of them syntheses that pooled 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.
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.
An Open-label, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Doxorubicin in Combination With Radiotherapy, Temozolomide and Valproic Acid in Patients With Glioblastoma Multiforme (GBM) and Diffuse Intrinsic Pontine Glioma (DIPG)
Who cites it
128 citing papers in PubMed, 4 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Repurposing neurological drugs for brain cancer therapeutics: A systematic approach to identify charged molecules for affinity-based local drug delivery systems.International journal of pharmaceutics · 2025Pooled it
- Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.Journal of neuro-oncology · 2020Pooled it
- Management of epilepsy in brain tumors.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Guideline
- Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.Translational research : the journal of laboratory and clinical medicine · 2019Pooled it
- 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 · 2024Trial
- Phase I/II trial of vorinostat combined with temozolomide and radiation therapy for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02.Neuro-oncology · 2018Trial
- Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma.Oncotarget · 2017Trial
- Postoperative Seizure Prophylaxis in Intracranial Tumors: Evaluating the Role of Anti-Seizure Medication in Seizure-Naïve Patients.Current neurology and neuroscience reports · 2026Review
- Review
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Dynamic susceptibility contrast perfusion in differentiation between recurrence and pseudoprogression in glioblastoma: a systematic review and meta-analysis.Quantitative imaging in medicine and surgery · 2025Article
- Methylation-induced suppression of YAP/TAZ confers sensitivity to HDAC inhibitors in high-grade IDH mutant gliomas.JCI insight · 2025Article
- Serum p-Cresol and 7-HOCA Levels and Fatty Acid and Purine Metabolism Are Associated with Survival, Progression, and Molecular Classification in GB-Serum Proteome and Metabolome Analysis Pre vs. Post Up-Front Chemoirradiation.Current oncology (Toronto, Ont.) · 2025Article
- Neural Vulnerabilities in Glioblastoma: Rethinking Therapy Through Neuroactive Drug Repurposing.Brain tumor research and treatment · 2025Review
- Brain Tumor Related Epilepsy: Pathophysiology and Multimodal Approach to Management.Current oncology reports · 2025Review
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Metabolic traits shape responses to LSD1-directed therapy in glioblastoma tumor-initiating cells.Science advances · 2025Article
- Review
- Nanophotonic-enhanced photoacoustic imaging for brain tumor detection.Journal of nanobiotechnology · 2025Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeValproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. METHODS AND MATERIALS: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment).
resultsA total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels.
conclusionsAddition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.
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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.