Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas

Clinical article

Restricted access

Object

Seizures occur in approximately 80% of patients with low-grade gliomas (LGGs). The majority of patients are treated with anticonvulsant monotherapy; however, many patients require multidrug therapy, or their seizures are refractory to antiepileptic drugs altogether. The oral alkylating agent temozolomide has emerged as a potential initial treatment option for LGG. A few reports suggest an association between temozolomide and reduced seizure frequency in patients with intractable epilepsy.

Methods

Using their clinical database, the authors identified adult patients whose LGGs were treated using temozolomide as the initial antineoplastic therapy at the University of Virginia Health System. As a control group, the authors assessed patients whose LGGs were under observation. All patients had seizure disorders that were treated with anticonvulsants. Seizure frequency in patients with intractable epilepsy was analyzed before and after treatment with temozolomide. Age at diagnosis, sex, antiepileptic drugs, pathological subtype, surgical treatment, and follow-up until progression were also assessed. Interval seizure frequency was meticulously analyzed at each neurooncology clinic visit. A meaningful difference in seizures was defined as a reduction in seizure frequency of greater than 50% per month.

Results

Thirty-nine patients were identified in the temozolomide cohort and 30 patients in the control cohort. The median age at diagnosis was 46 years for the former cohort and 41.5 years for the latter. The median length of follow-up was 39 months for the temozolomide group and 37 months for the control group. There was a significant difference in reduced seizure frequency between patients receiving temozolomide (59%) and those who did not receive temozolomide (13%, p < 0.001). Seven patients (18%) in the temozolomide group displayed this improvement independent of antiepileptic drug adjustment compared with no patient in the control group (p < 0.001).

Conclusions

The authors' data suggest that a subset of patients with LGGs experience improvement in seizure frequency during treatment with temozolomide independent of antiepileptic drug adjustment. This decrease in seizure frequency appears independent of the natural history of seizures in patients whose tumors are under observation. Consequently, seizures in patients with LGGs may be better controlled with the combination of AEDs and temozolomide.

Abbreviations used in this paper: AED = antiepileptic drug; LGG = low-grade glioma.

Article Information

Address correspondence to: Jonathan H. Sherman, M.D., 200 East 72nd Street, Apartment 18A, New York, New York 10021. email: jsherman0620@gmail.com.

Please include this information when citing this paper: published online January 14, 2011; DOI: 10.3171/2010.12.JNS101602

© AANS, except where prohibited by US copyright law.

Headings

References

  • 1

    Berger MSGhatan SHaglund MMDobbins JOjemann GA: Low-grade gliomas associated with intractable epilepsy: seizure outcome utilizing electrocorticography during tumor resection. J Neurosurg 79:62691993

  • 2

    Brada MViviers LAbson CHines FBritton JAshley S: Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 14:171517212003

  • 3

    Cairncross JGUeki KZlatescu MCLisle DKFinkelstein DMHammond RR: Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:147314791998

  • 4

    Chaichana KLMcGirt MJLaterra JOlivi AQuiñones-Hinojosa A: Recurrence and malignant degeneration after resection of adult hemispheric low-grade gliomas. Clinical article. J Neurosurg 112:10172010

  • 5

    Chalifoux RElisevich K: Effect of ionizing radiation on partial seizures attributable to malignant cerebral tumors. Stereotact Funct Neurosurg 67:1691821997

  • 6

    Chang EFPotts MBKeles GELamborn KRChang SMBarbaro NM: Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 108:2272352008

  • 7

    Haglund MMBerger MSKunkel DDFranck JEGhatan SOjemann GA: Changes in gamma-aminobutyric acid and somatostatin in epileptic cortex associated with low-grade gliomas. J Neurosurg 77:2092161992

  • 8

    Hildebrand JLecaille CPerennes JDelattre JY: Epileptic seizures during follow-up of patients treated for primary brain tumors. Neurology 65:2122152005

  • 9

    Janny PCure HMohr MHeldt NKwiatkowski FLemaire JJ: Low grade supratentorial astrocytomas. Management and prognostic factors. Cancer 73:193719451994

  • 10

    Keles GELamborn KRBerger MS: Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome. J Neurosurg 95:7357452001

  • 11

    Klein MEngelberts NHvan der Ploeg HMKasteleijn-Nolst Trenité DGAaronson NKTaphoorn MJ: Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life. Ann Neurol 54:5145202003

  • 12

    Lopes MBLaws ER Jr: Low-grade central nervous system tumors. Neurosurg Focus 12:2E12002

  • 13

    Luyken CBlümcke IFimmers RUrbach HElger CEWiestler OD: The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects. Epilepsia 44:8228302003

  • 14

    Ngo LNei MGlass J: Temozolomide treatment of refractory epilepsy in a patient with an oligodendroglioma. Epilepsia 47:123712382006

  • 15

    Okamoto YDi Patre PLBurkhard CHorstmann SJourde BFahey M: Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol 108:49562004

  • 16

    Pace AVidiri AGaliè ECarosi MTelera SCianciulli AM: Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann Oncol 14:172217262003

  • 17

    Pasquier BPéoc'h MFabre-Bocquentin BBensaadi LPasquier DHoffmann D: Surgical pathology of drug-resistant partial epilepsy. A 10-year-experience with a series of 327 consecutive resections. Epileptic Disord 4:991192002

  • 18

    Recht LDGlantz MNeoplastic diseases. Engel J JrPedley TA: Epilepsy: A Comprehensive Textbook ed 2PhiladephiaLippincott Williams & Wilkins2008. 3:26372642

  • 19

    Rogers LRMorris HHLupica K: Effect of cranial irradiation on seizure frequency in adults with low-grade astrocytoma and medically intractable epilepsy. Neurology 43:159916011993

  • 20

    Schiff DBrown PDGiannini C: Outcome in adult low-grade glioma: the impact of prognostic factors and treatment. Neurology 69:136613732007

  • 21

    van den Bent MJAfra Dde Witte OBen Hassel MSchraub SHoang-Xuan K: Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366:9859902005

  • 22

    van Veelen MLAvezaat CJKros JMvan Putten WVecht C: Supratentorial low grade astrocytoma: prognostic factors, dedifferentiation, and the issue of early versus late surgery. J Neurol Neurosurg Psychiatry 64:5815871998

  • 23

    Vecht CJWilms EB: Seizures in low- and high-grade gliomas: current management and future outlook. Expert Rev Anticancer Ther 10:6636692010

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 139 139 17
Full Text Views 155 155 1
PDF Downloads 72 72 1
EPUB Downloads 0 0 0

PubMed

Google Scholar