Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-24T13:28:33.971Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
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

References

REFERENCES

1. Bullard, DE, Rawlings, CE 3rd, Phillips, B, et al. Oligodendroglioma: an analysis of the value of radiation therapy. Cancer 1987;60:2179–2188.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
2. Byrne, TN, Cascino, TL, Posner, JB. Brain metastases from melanoma. J Neuro-onc 1983;1:313–317.Google Scholar
3. Cairncross, G, Posner, JB. The management of brain metastases. In: Walker, MD, Ed. Oncology of the Nervous System. Mass: Martinus Nighoff, 1983:341–378.Google Scholar
4. Cascino, TL, Leavengood, JM, Kemeny, N, Posner, JB. Brain metastases from colon cancer. J Neuro-onc 1983;1:203–209.Google Scholar
5. Clouston, PD, Deangelis, LM, Posner, JB. The spectrum of neurologic disease in patients with systemic cancer. Ann Neurol 1992;31: 268–273.Google Scholar
6. Gilbert, MR, Grossman, SA. Incidence and nature of neurologic problems in patients with solid tumours. Am J Med 1986;81:951–954.Google Scholar
7. Glantz, MJ, Cole, BF, Friedberg, MH, et al. A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumours. Neurology 1996;46:985–991.CrossRefGoogle Scholar
8. Hagen, NA, Cirrincione, C, Thaler, HT, Deangelis, LM. The role of radiation therapy following resection of single brain metastasis from melanoma. Neurology 1990;40:158–160.CrossRefGoogle ScholarPubMed
9. Hung, S, Hilsenbeck, S, Feun, L. Seizure prophylaxis with phenytoin in patients with brain metastases. Proceed ASCO 1991;10:327 (Abstract).Google Scholar
10. Jacobs, M, Phuphanich, S. Seizures in brain metastasis and meningeal carcinomatosis. Proceed ASCO 1990;9:96 (Abstract).Google Scholar
11. Lund, M. Epilepsy in association with intracranial tumours. Acta Psychiatr Neurol Scand 1952;8(Suppl):1–149.Google Scholar
12. Ludwig, CL, Smith, MT, Godfrey, AD, Armbrustmacher, AW. A clinico-pathological study of 323 patients with oligodendrogliomas. Ann Neurol 1986;19:15–21.Google Scholar
13. Paillas, JE, Pellet, W. Brain metastases. In: Vinken, PJ, Bruyn, GW, (Eds) Handbook of Neurology. Amsterdam: North Holland 1975:201–232.Google Scholar
14. Posner, JB. Management of central nervous system metastases. Semin Oncol 1977;4:81–91.Google Scholar
15. Shaw, ES, Scheithauer, BW, O’Fallon, JR, Tazelar, HD, Davis, DH. Oligodendroglioma: the Mayo Clinic experience. J Neurosurg 1992;76:428–439.Google Scholar
16. Simionescu, MD. Metastatic tumours of the brain: a follow-up study of 195 patients with neurosurgical considerations. J Neurosurg 1960;17:361–373.Google Scholar
17. Walker, MD, Green, SB, Byar, DP. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. New Eng J Med 1980;303:1323–1329.Google Scholar
18. Bardana, EJ, Gabourel, JD, Davies, GH, Craig, S. Effects of phenytoin on man’s immunity: evaluation of changes in serum immunoglobulins, complement, and anti-nuclear antibody. Am J Med 1983;74:289–296.Google Scholar
19. Delattre, J, Safai, B, Posner, JB. Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology 1988;38:194–198.Google Scholar
20. Haque, N, Thrasher, K, Werk, EE Jr, Knowles, HC Jr, Sholiton, LJ. Studies on dexamethasone metabolism in man: effect of diphenylhydantoin. J Clin Endocr 1972;34:44–50.CrossRefGoogle ScholarPubMed
21. Kikuchi, K, McCormick, CI, Neuwelt, EA. Immunosuppression by phenytoin: implication for altered immune competence in brain tumour patients. J Neurosurg 1984;61:1085–1090.CrossRefGoogle Scholar
22. Taylor, LP, Posner, JB. Phenobarbital rheumatism in patients with brain tumours. Ann Neurol 1989;25:92–94.Google Scholar
23. Bollini, P, Riva, R, Albani, F, et al. Decreased phenytoin level during antineoplastic therapy: a case report. Epilepsia 1983;24:75–78.CrossRefGoogle ScholarPubMed
24. Chalk, JB, Ridgeway, K, Brophy, T, Yelland, JD, Eadie, MJ. Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients. J Neurol Neurosurg Psych 1984;47:1087–1090.Google Scholar
25. Wong, DD, Longenecker, RG, Liepman, M, Baker, S, Lavergne, M. Phenytoin-dexamethasone: a possible drug interaction. JAMA 1985;254:2062–2063.CrossRefGoogle Scholar
26. Boarini, DJ, Beck, DW, Vangilder, JC. Postoperative prophylactic anticonvulsant therapy in cerebral gliomas. Neurosurg 1985;16:290–292.CrossRefGoogle ScholarPubMed
27. Mahaley, MS, Dudka, L. The role of anticonvulsants in the management of patients with anaplastic gliomas. Surg Neurol 1981;16:399–401.Google Scholar
28. Penfield, W, Erickson, TC, Tarlov, I. Relation of intracranial tumours and symptomatic epilepsy. Arch Neurol Psych 1940;44:300–315.CrossRefGoogle Scholar
29. Rasmussen, T, Blundell, J. Epilepsy and brain tumours. Clin Neurosurg 1959;7:38–158.Google Scholar
30. Sachs, E, Furlow, LT. The significance of convulsions in the diagnosis of brain tumours. J Mo State Med Assoc 1936;33:121–127.Google Scholar
31. Daumas-Duport, C, Scheithauer, BW, Chodkiewicz, JP, Laws, ER, Vedrenne, C. Dysembryoplastic neuroepithelial tumours: a surgically curable tumour of young patients with intractable partial seizures. Neurosurgery 1988;23:545–556.CrossRefGoogle ScholarPubMed
32. Forsyth, PA, Shaw, E, Scheithauer, B, Layton, D, O’Fallan, J. 51 cases of supratentorial pilocytic astrocytoma: a clinicopathologic, prognostic and flow-cytometric study. Cancer 1993;72:1335–1342.Google Scholar
33. Kalyan-Raman, UP, Olivero, WC. Ganglioglioma: a correlative clinicopathological and radiological study of ten surgically treated cases with follow-up. Neurosurgery 1987;20:428–433.CrossRefGoogle ScholarPubMed
34. Kepes, JJ, Rubinstein, LJ, Eng, LF. Pleomorphic xanthoastrocytoma: a distinctive meningocerebral glioma of young subjects with a relatively favourable prognosis. Cancer 1979;44:1839–1852.3.0.CO;2-0>CrossRefGoogle Scholar
35. Piepmeier, JM. Observations on the current treatment of low-grade astrocytic tumours of the cerebral hemispheres. J Neurosurg 1987;67:177–181.CrossRefGoogle ScholarPubMed
36. Whitton, AC, Bloom, HJG. Low-grade glioma of the cerebral hemispheres in adults: a retrospective analysis of 88 cases. Int J Radiat Oncol Bio Phys 1990;18:783–786.Google Scholar
37. Glantz, MJ, Cole, BF, Forsyth, PA, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumours. Neurology 2000;54:1886–1893.CrossRefGoogle Scholar
38. North, JB, Penhall, RK, Hanieh, A, Frewin, DB, Taylor, WB. Phenytoin and postoperative epilepsy: a double blind study. J Neurosurg 1983;58:672–677.CrossRefGoogle ScholarPubMed
39. Franceschetti, S, Binelli, S, Casazza, M, et al. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Acta Neurochir 1990;103:47–51.CrossRefGoogle ScholarPubMed