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Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients

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Summary

Seizures are a common complication of primary (PBT) and metastatic (MBT) brain tumors, affecting approximately 50% of all patients during the course of their illness. Anti-convulsant therapy of these tumor-induced seizures is often inadequate with conventional anti-epileptic drugs (AEDs), due to a variety of factors, including activation of glutaminergic NMDA receptors, immune-mediated neuronal damage, and anatomic alterations of neuronal input pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action, which includes reducing the Ca++ current through neuron-specific, high voltage activated Ca++ channels (n-type). Because of this unique mechanism, it has been postulated that LEV may be effective in controlling tumor-induced seizures. A retrospective chart review was performed of all patients who had received LEV for seizure control. Forty-one patients were reviewed (22 female, 19 male), with a median age of 47.5 years (range 25–81). There were 34 patients with PBT and 7 with MBT. LEV was used as an add-on AED in 33 patients and as monotherapy in eight patients, with a median dose of 1500 mg/day (range 500–3500). The baseline median seizure frequency for the cohort was 1 per week. After the addition of LEV and follow-up for a minimum of 4 weeks, the median seizure frequency was reduced to 0 per week (59% of patients noted complete seizure control). Overall, the seizure frequency was reduced in 90% of patients (P<0.0001; Sign test). The most common toxicity was somnolence, noted in 37% of patients. LEV was very effective and well tolerated in brain tumor patients with seizures, and should be considered for add-on therapy to current AEDs, or as a substitute anti-convulsant for monotherapy.

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References

  1. Newton HB, 1994 Primary brain tumors: Review of etiology, diagnosis, and treatment Am Fam Phys 49: 787–797

    CAS  Google Scholar 

  2. Newton HB, 1999 Neurological complications of systemic cancer Am Fam Phys 59: 878–886

    CAS  Google Scholar 

  3. Glantz M, Recht LD, 1997 Epilepsy in the cancer patient. In: Vecht C.J., (ed.) Handbook of Clinical Neurology Vol. 25 Elsevier Science Amsterdam, pp 9–18

    Google Scholar 

  4. Bromfield EB, 2004 Epilepsy in patients with brain tumors and other cancers Rev Neurol Dis 1: S27–S33

    PubMed  Google Scholar 

  5. Schaller B, Ruegg SJ, 2003 Brain tumor and seizures: pathophysiology and its implications for treatment revisited Epilepsia 44: 1223–1232

    Article  PubMed  Google Scholar 

  6. Tan B, Piwinica-Worms D, Ratner L, 2000 Multidrug resistance transporters and modulation Curr Opin Oncol 12: 450–458

    Article  PubMed  CAS  Google Scholar 

  7. French JA, Kanner AM, Bautista J, et al 2004a Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy Neurol 62: 1252–1260

    CAS  Google Scholar 

  8. French JA, Kanner AM, Bautista J, et al 2004b Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy Neurol. 62: 1261–1273

    CAS  Google Scholar 

  9. Patsalos PN, 2000 Pharmacokinetic profile of levetiracetam: toward ideal characteristics Pharmacol Ther 85: 77–85

    Article  PubMed  CAS  Google Scholar 

  10. Lynch BA, Lambeng N, Nocka K, et al 2004 The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam Proc Natl Acad Sci 101: 9861–9866

    Article  PubMed  CAS  Google Scholar 

  11. Niespodziany I, Klitgaard H, Margineanu DG, 2000 Levetiracetam: modulation of high voltage activated Ca++ current in CA1 pyramidal neurons of rat hippocampal slices (abstract) Epilepsia 41: 37

    Article  Google Scholar 

  12. Lukyanetz EA, Shkryl VM, Kostyuk PG, 2002 Selective blockade of N-type calcium channels by levetiracetam Epilepsia 43:9–18

    Article  PubMed  CAS  Google Scholar 

  13. Zona C, Niespodziany I, Marchetti C, Klitgaard H, Bernardi G, Margineanu DG, 2001 Levetiracetam does not modulate neuronal voltage-gated Na+ and T-type Ca++ currents Seizure 10: 279–286

    Article  PubMed  CAS  Google Scholar 

  14. Rigo JM, Hans G, Nguyen L, et al, 2002 The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine -gated currents Br J Pharmacol 136: 59–672

    Article  Google Scholar 

  15. Wagner GL, Wilms EB, Van Donselaar CA, Vecht CJ, 2003 Levetiracetam: preliminary experience in patients with primary brain tumors Seizure 12: 585–586

    Article  PubMed  CAS  Google Scholar 

  16. Elisevich K, 1999 Epilepsy and low-grade gliomas. In: Rock JP, Rosenblum ML, Shaw EG, Cairncross JG, (eds.), The Practical Management of Low-Grade Primary Brain Tumors Vol. 10 Lippincott Williams & Wilkins Philadelphia, pp 149–169

    Google Scholar 

  17. Alsaadi TM, Shatzel A, Marquez AV, Jorgensen J, Farias S, 2005 Clinical experience of levetiracetam monotherapy for adults with epilepsy: 1-year follow-up study Seizure 14: 139–142

    Article  PubMed  Google Scholar 

  18. Habetswallner F, Fels A, Pagliuca M, De Joanna G, Rossi V, Tessitore A, 2005 Levetiracetam as monotherapy for partial epilepsy in adults: A case series (abstract) Eur J Neurol 12: 121–122

    Article  Google Scholar 

  19. Kivisto KT, Kroemer HK, Eichelbaum M, 1995 The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions Br J Clin Pharmacol 40: 523–530

    PubMed  CAS  Google Scholar 

  20. Vecht CJ, Wagner GL, Wilms EB, 2003a Treating seizures in patients with brain tumors: drug interactions between antiepileptic and chemotherapeutic agents Semin Oncol 30: 49–52

    Article  CAS  Google Scholar 

  21. Vecht CJ, Wagner GL, Wilms EB, 2003b Interactions between antiepileptic and chemotherapeutic drugs Lancet Neurol 2: 404–409

    Article  CAS  Google Scholar 

  22. Fetell MR, Grossman SA, Fisher JD, et al 1997 Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions J Clin Oncol 15: 3121–3128

    PubMed  CAS  Google Scholar 

  23. Villikka K, Kivisto KT, Maenpaa H, Joensuu H, Neuvonen PJ, 1999 Cytochrome P450-inducing antiepileptics increase the clearance of vincristine in patients with brain tumors Clin Pharmacol Ther 66: 589–593

    PubMed  CAS  Google Scholar 

  24. Riva M, Landonio G, Defanti CA, Siena S, 2000 The effect of anticonvulsant drugs on blood levels of methotrexate J Neuro-Oncol 48: 249–250

    Article  CAS  Google Scholar 

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Acknowledgements

The Authors would like to thank Ryan Smith for research assistance. Dr. Newton was supported in part by an unrestricted Clinical Grant from UCB Pharma, Inc., National Cancer Institute Grant, CA 16058, and the Esther Dardinger Neuro-Oncology Center Endowment Fund.

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Correspondence to Herbert B. Newton.

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Newton, H.B., Goldlust, S.A. & Pearl, D. Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. J Neurooncol 78, 99–102 (2006). https://doi.org/10.1007/s11060-005-9070-4

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  • DOI: https://doi.org/10.1007/s11060-005-9070-4

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