Is valproic acid effective for glioblastoma treatment?
['A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma.', 'PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models.', ' Median overall survival (OS) was 29.6\xa0months (range: 21-63.8\xa0months), and median progression-free survival (PFS) was 10.5\xa0months (range: 6.8-51.2\xa0months). OS at 6, 12, and 24\xa0months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24\xa0months was 70%, 43%, and 38% respectively. ', 'CONCLUSIONS: Addition 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.', 'Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs.', 'Several clinical studies have reported that valproic acid could prolong survival of GBM patients. ', 'Our meta-analysis confirmed the benefit of using VPA (HR, 0.56; 95% CI, 0.44-0.71). Sub-group analysis shows that patients treated with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59-0.94 vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95% confidence interval of 0.52-0.84 vs. patients treated by administration of non-AEDs. ', '.CONCLUSION: The results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration. ', 'A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. ', 'Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models', 'Valproic acid use during radiation therapy for glioblastoma associated with improved survival', '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)', 'Valproic acid use during radiation therapy for glioblastoma associated with improved survival.', 'Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.', 'PURPOSE: 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).METHODS AND MATERIALS: 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.RESULTS: 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. ', '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.', 'Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.', "Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM."]
['Yes, valproic acid prolong survival of glioblastoma patients. Valproic acid is an antiepileptic agent with histone deacetylase inhibitor activity shown to sensitize glioblastoma cells to radiation in preclinical models.']
['yes']