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Prophylactic Anticonvulsants in Patients with Brain Tumour

Published online by Cambridge University Press:  16 December 2016

Peter A. Forsyth ,
Susan Weaver ,
Dorcas Fulton ,
Penelope M.A. Brasher ,
Garnette Sutherland ,
Doug Stewart ,
Neil A. Hagen ,
Penny Barnes ,
J. Greg Cairncross  and
Lisa M. DeAngelis
Peter A. Forsyth*
Affiliation:
Departments of Oncology & Clinical Neurosciences, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta
Susan Weaver
Affiliation:
Departments of Neurology and Medicine, Albany Medical College, Albany, New York
Dorcas Fulton
Affiliation:
Department of Radiation Oncology, Cross Cancer Institute and Department of Medicine/Neurology, University of Alberta, Edmonton
Penelope M.A. Brasher
Affiliation:
Department of Epidemiology, Prevention & Screening, Tom Baker Cancer Centre
Garnette Sutherland
Affiliation:
Division of Neurosurgery, Department of Clinical Neurosciences, The University of Calgary, Calgary, Alberta
Doug Stewart
Affiliation:
Departments of Oncology & Clinical Neurosciences, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta
Neil A. Hagen
Affiliation:
Departments of Oncology & Clinical Neurosciences, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta
Penny Barnes
Affiliation:
Departments of Oncology & Clinical Neurosciences, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta
J. Greg Cairncross
Affiliation:
Departments of Oncology & Clinical Neurosciences, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta
Lisa M. DeAngelis
Affiliation:
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
*
Department of Medicine, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, Alberta Canada T2N 4N2
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Abstract:

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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

RÉSUMÉObjectif:

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'une étude prospective, ouverte, randomisée. Soixante patients avaient une maladie métastatique et quarante avaient une tumeur cérébrale primitive. Quarante-six (46%) des patients ont été randomisés au groupe AC et 54 (54%) au groupe sans AC. Le suivi médian a été de 5,44 mois (écart de 0,13 à 30,1 mois).

Résultats:

Vingt-six patients ont présenté des crises (26%), onze dans le groupe AC et 15 dans le groupe sans AC. La survie sans crise n'était pas différente: à trois mois, 87% des patients du groupe AC et 90% de ceux du groupe sans AC n'avaient pas présenté de crise (test du log-rang, p=0,98). Soixante-dix patients sont décédés (décès non reliés à une crise convulsive) et les taux de survie étaient équivalents dans les deux groupes (survie médiane de 6,8 mois versus 5,6 mois respectivement; test du log-rang p=0,50). Nous avons limité le recrutement à 100 patients parce que le taux de crise et de survie étaient beaucoup plus bas que prévu: nous aurions eu besoin de plus de 900 patients pour que l'étude ait une puissance statistique suffisante.

Conclusions:

Ces données devraient être utilisées par ceux qui se proposent de faire un essai thérapeutique pour déterminer si les anticonvulsivants prophylactiques sont efficaces dans des sous-groupes de patients atteints de tumeurs cérébrales (e.g. seulement des astrocytomes anaplasiques). Quand ces résultats sont considérés conjointement avec ceux d'un essai thérapeutique similaire, il est peu probable que les anticonvulsivants prophylactiques soient efficaces ou utiles chez les patients porteurs de tumeurs cérébrales qui n'ont pas eu de crise.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 30 , Issue 2 , May 2003 , pp. 106 - 112
Copyright
Copyright © The Canadian Journal of Neurological 2003

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