The role of anticonvulsant medications in the management of patients with anaplastic gliomas

Mahaley, M. S.; Dudka, Lynn

doi:10.1016/0090-3019(81)90227-5

Cited by 70 publications

(39 citation statements)

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“…Seizures are more common in slowly growing tumours [31][32][33][34][35][36] but less so in more malignant ones. 17,27 A complicating issue is the risk of postoperative seizures because all patients undergo craniotomies or biopsies for diagnosis. Retrospective studies 26,27 of patients with malignant supratentorial gliomas found no significant reduction of postoperative seizures with prophylactic anticonvulsants.…”

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“…17,27 A complicating issue is the risk of postoperative seizures because all patients undergo craniotomies or biopsies for diagnosis. Retrospective studies 26,27 of patients with malignant supratentorial gliomas found no significant reduction of postoperative seizures with prophylactic anticonvulsants. The only other prospective randomized trial of prophylactic anticonvulsants in patients with brain tumour (published after we began our trial) found seizure prophylaxis ineffective.…”

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confidence: 99%

“…Seizure risk is related to tumour location, particularly frontal and parietal lobes 11,[26][27][28][29][30] and their rate of growth. Seizures are more common in slowly growing tumours [31][32][33][34][35][36] but less so in more malignant ones.…”

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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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Prophylactic Anticonvulsants in Patients with Brain Tumour

Forsyth

Weaver

Fulton

et al. 2003

Can. j. neurol. sci.

159

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“…[50][51][52] Twenty to 40% of all brain tumor patients have experienced a seizure by the time their brain tumor is diagnosed. 3,4,11,12,[14][15][16][53][54][55][56][57][58][59][60][61] In these patients, the need for anticonvulsant medication is clear. Patients who have not experienced a seizure remain at risk, however, and at least 20 to 45% more (depending on factors such as tumor histology, location, age, and treatment) will ultimately develop seizures.…”

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Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors [RETIRED]

et al. 2000

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Overview. The Quality Standards Subcommittee seeks to develop scientifically sound, clinically relevant practice parameters for the practice of neurology. Practice parameters are strategies for patient management that assist physicians in clinical decision making. A practice parameter is one or more specific recommendations based on analysis of evidence on a specific clinical problem. These might include diagnosis, symptoms, treatment, or procedure evaluation. American Academy of Neurology (AAN) members have requested the publication of a practice parameter on the use of prophylactic anticonvulsants in patients with primary and metastatic brain tumors.Justification. Physicians often administer anticonvulsant medication prophylactically to patients with brain tumors, despite the lack of definitive evidence that prophylactic anticonvulsant therapy is effective in preventing first seizures. [1][2][3][4] If anticonvulsant medications were free of side effects, their prophylactic use might be attractive even without such evidence. However, discomfort, expense, and inconvenience result from drug treatment and periodic monitoring of serum drug concentrations. Typical anticonvulsant-induced side effects, including cognitive impairment, myelosuppression, liver dysfunction, and dermatologic reactions (ranging from minor rashes to life-threatening Stevens-Johnson syndrome), appear to occur more frequently in patients with brain tumors than in other patient groups, 3,5-16 although direct comparison studies have not been published. A spectrum of side effects unique to patients with brain tumors must also be considered. Phenytoin, carbamazepine, and phenobarbital reduce the efficacy of corticosteroids, 17-21 which are administered almost universally to brain tumor patients. In addition, the ability of these anticonvulsants to stimulate the cytochrome P450 enzyme system results in markedly accelerated metabolism of a wide spectrum of chemotherapeutic agents including nitrosoureas, paclitaxel, cyclophosphamide, topotecan, irinotecan, thiotepa, 9-aminocampo-thecin, adriamycin, and methotrexate.22-34 As a result, inadequate chemotherapeutic dosing of brain tumor patients has been identified recently as a widespread and critically important problem. 35 Conversely, corticosteroids and many chemotherapeutic agents alter the metabolism of anticonvulsants, making anticonvulsant under-and overdosing more common. [35][36][37][38][39][40][41][42][43][44][45] The potential immunosuppressive effect of anticonvulsant medications represents an additional risk to this already immunocompromised patient population. [46][47][48][49] In 1998, more than 170,000 patients were diagnosed with brain metastases, and more than 34,000 developed primary brain tumors. [50][51][52] Twenty to 40% of all brain tumor patients have experienced a seizure by the time their brain tumor is diagnosed. 3,4,11,12,[14][15][16][53][54][55][56][57][58][59][60][61] In these patients, the need for anticonvulsant medication is clear. Patients who have not experienced a seiz...

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“…Postoperative antiepileptic medical prophylaxis is advised for patients with supratentorial gliomas. In a study of anaplastic gliomas, 36% of patients without preoperative indication of epileptogenicity experienced a postoperative seizure [86]. In a nonrandomized study, the incidence of all seizure types was lower in the early postoperative stage (21% vs 39%) in patients receiving antiepileptic treatment compared with those left untreated [87].…”

Section: Antiepileptic Medical Managementmentioning

confidence: 99%

Glioma-Associated Epilepsy

Elisevich¹

2013

Clinical Management and Evolving Novel Therapeutic Strategies for Patients With Brain Tumors

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The role of anticonvulsant medications in the management of patients with anaplastic gliomas

Cited by 70 publications

References 2 publications

Prophylactic Anticonvulsants in Patients with Brain Tumour

Prophylactic Anticonvulsants in Patients with Brain Tumour

Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors [RETIRED]

Glioma-Associated Epilepsy

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