Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme

Kerkhof, Marjon; Dielemans, Janneke; Breemen, Melanie S. van; Zwinkels, Hanneke; Walchenbach, R.; Taphoorn, Martin J.B.; Vecht, Charles J.

doi:10.1093/neuonc/not057

Cited by 193 publications

(171 citation statements)

References 30 publications

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“…No significant difference in terms of PFS was observed. In the study performed by Kerkhof et al [16] patients with GBM using VPA in combination with TMZ/RT showed a longer median survival of 69 weeks compared with 61 weeks in the group without VPA after adjusting for age, extent of resection and MGMT methylation status. Another study [15] has reported that VPA use during RT for GBM was associated with improved OS, independently of RTOG, RPA class, seizure history and concurrent TMZ use.…”

mentioning

confidence: 95%

“…Some retrospective clinical studies [4,[14][15][16] and a meta-analysis of individual patient data [17] have suggested that VPA could prolong overall survival in adult patients with GBM. Oberndorfer and collegues [4] investigated the effects of EI-AEDs or non-EIAEDs on survival in 168 patients with GBM treated with surgery, radiotherapy and chemotherapy (either CCNU or TMZ).…”

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confidence: 99%

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Does valproic acid affect tumor growth and improve survival in glioblastomas?

Rudà¹,

Pellerino²,

Soffietti³

2016

CNS Oncol.

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confidence: 95%

mentioning

confidence: 99%

Does valproic acid affect tumor growth and improve survival in glioblastomas?

Rudà¹,

Pellerino²,

Soffietti³

2016

CNS Oncol.

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“…Besides, it seems preferable to avoid AEDs on which there are hardly any data available in brain tumors. For that reason, the monotherapy drugs of first choice are the evidence-based agents levetiracetam and valproic acid for focal epilepsy and for which use in EBT many data are available (Hildebrand et al, 2005;Oberndorfer et al, 2005;Lim et al, 2009;van Breemen et al, 2009;Merrell et al, 2010b;Weller et al, 2011;Kerkhof et al, 2013;Vecht et al, 2014).…”

Section: Antiepileptic Drug Therapymentioning

confidence: 99%

“…In GBM, about 40-45% of patients present with epilepsy, often as secondary generalized seizure, while 15-20% develop seizures later on (Moots et al, 1995;Kerkhof et al, 2013). Smaller tumors and those growing less quickly are associated with higher rates of seizures than large, rapidly growing lesions (Moots et al, 1995;Glantz et al, 2000;Herman, 2002;Pasquier et al, 2002;Rosati et al, 2009;Chaichana et al, 2009b;Lee et al, 2010).…”

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confidence: 99%

Epilepsy and Brain Tumors

Newton

Maschio²,

Pritikin³

2015

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Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70-80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60-75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20-50% of patients with meningioma and 20-35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60-90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life.

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“…More recently it has been appreciated that VPA is a histone deacetylase inhibitor (HDACi) [11]; these have been explored as candidate radio-sensitizers in a variety of cancers [12]. Retrospective data from trials of specific HDACis and specifically with valproate in brain cancer patients have suggested efficacy [13][14][15][16].…”

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confidence: 99%

Where is the radiobiology and pharmacology research to improve outcomes in glioblastoma?

2015

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Personalized medicine has been helpful for drug development in diseases with single and relatively stable gene mutations. The benefit for complex solid tumours with heterogeneous and changing genetic profiles is less clear. Whether it is efficient to continue diverting resources from combined biological and pharmacological approaches to trial new and existing genetic 'targeted therapies' for brain tumours is unknown but of developing concern in resource constrained environments.

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Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme

Abstract: Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.

Cited by 193 publications

References 30 publications

Does valproic acid affect tumor growth and improve survival in glioblastomas?

Does valproic acid affect tumor growth and improve survival in glioblastomas?

Epilepsy and Brain Tumors

Where is the radiobiology and pharmacology research to improve outcomes in glioblastoma?

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