A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors

Glantz, Michael; Cole, Bernard F.; Friedberg, Marc H.; Lathi, Ellen; Choy, Hak; Furie, Karen L.; Akerley, Wallace; Wahlberg, L. U.; Lekos, Andrew; Louis, Sydney

doi:10.1212/wnl.46.4.985

Cited by 202 publications

(116 citation statements)

References 19 publications

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“…Our data suggest that we could only rule out a risk reduction of more than 46% if patients took anticonvulsants prophylactically. However, when considered in conjunction with other randomized trials (or portions thereof 7,38,39 ), and a metaanalysis, 37 the results suggest prophylactic anticonvulsants are ineffective. The lower than expected seizure and survival rates we found in our patients suggested we needed to accrue ≥ 900 patients to have an adequately powered study; this was clearly not feasible or reasonable and we terminated the study.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Brain tumour patients who present with seizures are treated with anticonvulsants but these drugs are frequently used prophylactically. A generalized seizure may be lethal if it is prolonged or if the patient does not recover consciousness.…”

mentioning

confidence: 99%

“…The only other prospective randomized trial of prophylactic anticonvulsants in patients with brain tumour (published after we began our trial) found seizure prophylaxis ineffective. 7 This study used divalproex sodium as an anticonvulsant and randomized a smaller number of patients. The data we present here, and those from Glantz et al 7 were used to construct a practice parameter by the American Academy of Neurology (AAN) that recommends that prophylactic anticonvulsants not be used in patients with brain tumour.…”

mentioning

confidence: 99%

“…7 This study used divalproex sodium as an anticonvulsant and randomized a smaller number of patients. The data we present here, and those from Glantz et al 7 were used to construct a practice parameter by the American Academy of Neurology (AAN) that recommends that prophylactic anticonvulsants not be used in patients with brain tumour. 37 We think it is important that the details of our data be examined so that the basis and limitations of these recommendations be understood.…”

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confidence: 99%

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Prophylactic Anticonvulsants in Patients with Brain Tumour

Forsyth

Weaver

Fulton

et al. 2003

Can. j. neurol. sci.

159

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Seizures are reported to occur in at least 20% of patients with metastatic or primary brain tumour. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Brain tumour patients who present with seizures are treated with anticonvulsants but these drugs are frequently used prophylactically. A generalized seizure may be lethal if it is prolonged or if the patient does not recover consciousness. [18][19][20][21][22] Seizures may cause unacceptable toxicity or interact with other drugs, such as corticosteroids [23][24][25] or chemotherapeutic agents which may compromise the patient's overall treatment. Retrospective studies of prophylactic anticonvulsants in patients with metastases have been conflicting ABSTRACT: Objective: We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. Methods: One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Results: Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need ≥ 900 patients to have a suitably powered study. Conclusions: These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure.RÉSUMÉ: Une question importante en neuro-oncologie à la quelle il est difficile de répondre: l'utilité des anticonvulsivants prophylactique chez les patients porteurs d'une tumeur cérébrale. Objectif: Nous avons procédé à un essai thérapeutique pour déterminer si les anticonvulsivants administrés de façon préventive chez les patients porteurs d'une tumeur cérébrale, sans épisode convulsif antérieur, réduisent la fréquence des crises épileptiques. Nous avons limité le recrutement à 100 patients suite à une analyse intérimaire. Méthodes: Cent patients, atteints de tumeurs cérébrales dont le diagnostic était récent, ont reçu des anticonvulsivants (groupe AC) ou n'en ont pas reçu (groupe sans AC) dans le cadre d'un...

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Section: Discussionmentioning

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Prophylactic Anticonvulsants in Patients with Brain Tumour

Forsyth

Weaver

Fulton

et al. 2003

Can. j. neurol. sci.

159

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“…Randomized prospective studies have found no significant reduction in the incidence of first seizures in brain tumor patients placed on prophylactic anticonvulsants. [35][36][37] New onset of seizures was experienced by approximately 25% of patients treated with prophylactic anticonvulsants, not significantly different than the percentage of patients experiencing new onset of seizures in the control arm. The meta-analysis by Glantz et al 34 concluded that there was no evidence that prophylactic anticonvulsants significantly decreased the incidence of first seizure.…”

Section: Prophylactic Anticonvulsantsmentioning

confidence: 99%

ACR Appropriateness Criteria^® Pre-Irradiation Evaluation and Management of Brain Metastases

Gore

Bradley

et al. 2014

Journal of Palliative Medicine

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Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

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Efficacy and Safety of Levetiracetam in Patients With Glioma

Rosati¹,

Buttolo²,

Stefini³

et al. 2010

Arch Neurol

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A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors

Abstract: Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seizures.

Cited by 202 publications

References 19 publications

Prophylactic Anticonvulsants in Patients with Brain Tumour

Prophylactic Anticonvulsants in Patients with Brain Tumour

ACR Appropriateness Criteria^® Pre-Irradiation Evaluation and Management of Brain Metastases

Efficacy and Safety of Levetiracetam in Patients With Glioma

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A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors

Abstract: Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seizures.

Cited by 202 publications

References 19 publications

Prophylactic Anticonvulsants in Patients with Brain Tumour

Prophylactic Anticonvulsants in Patients with Brain Tumour

ACR Appropriateness Criteria® Pre-Irradiation Evaluation and Management of Brain Metastases

Efficacy and Safety of Levetiracetam in Patients With Glioma

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Product

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ACR Appropriateness Criteria^® Pre-Irradiation Evaluation and Management of Brain Metastases