Abstract
Seizures are a common complication of metastatic brain tumors (MBT), affecting approximately 27–50% of all patients during the course of their illness. Treatment of tumor-induced seizures is often inadequate with traditional antiepileptic drugs (AED) due to a variety of factors, including activation of glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A, that has been previously shown to reduce seizure activity in patients with primary brain tumors. Due to its unique mechanism of action, it has been postulated that LEV may also be effective in controlling seizures from MBT. A retrospective chart review was performed of all Neuro-Oncology Center patients with MBT who had received LEV for seizure control. Thirteen patients were reviewed with a median age of 55.1 years (range: 34–70). Six patients had breast cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED in seven patients (54%) and as monotherapy in six patients (46%), with a median dose of 1,000 mg/day (range: 500–3,000). The baseline median seizure frequency was one ictal event every other day. After the addition of LEV, the median seizure frequency was reduced to 0 per week. The seizure frequency was reduced to less than 50% of the pre-LEV baseline in 100% of patients (P = 0.0002, Sign test), with 10 patients (77%; confidence interval: 46–95%) noting complete seizure control. The most common adverse event was somnolence and headache, noted in 3 of 13 patients (23%). LEV was very effective and well tolerated in MBT patients with seizures and should be considered for add-on therapy or as a substitute AED for monotherapy.
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References
Arnold SM, Patchell RA (2001) Diagnosis and management of brain metastases. Hematol Oncol Clin North Am 15:1085–1107
Posner JB, Chernik NL (1978) Intracranial metastases from systemic cancer. Adv Neurol 19:579–592
Soffietti R, Ruda R, Mutani R (2002) Management of brain metastases. J Neurol 249:1357–1369
Oberndorfer S, Schmal T, Lahrmann H et al (2002) The frequency of seizures in patients with primary brain tumors or cerebral metastases. An evaluation from the Ludwig Boltzmann Institute of Neuro-Oncology and the Department of Neurology, Kaiser Franz Josef Hospital, Vienna. Wien Klin Wochenschr 114:911–916
Schaller B, Ruegg SJ (2003) Brain tumor and seizures: pathophysiology and its implications for treatment revisited. Epilepsia 44:1223–1232
Glantz MJ, Cole BF, Forsyth PA et al (2000) Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors-report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurol 54:1886–1893
El Kamar FG, Posner JB (2004) Brain metastases. Semin Neurol 24:347–362
Fetell MR, Grossman SA, Fisher JD et al (1997) Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin Oncol 15:3121–3128
Liddle C, Goodwin BJ, George J et al (1998) Separate and interactive regulation of cytochrome P450 3A4 by triidothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab 83:2411–2416
Patsalos PN (2000) Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther 85:77–85
Stevens GH (2005) Antiepileptic drug use in patients with brain tumors. Profiles in Seizure Manage 4:5–9
Stahl SM (2004) Psychopharmacology of anticonvulsants: levetiracetam as a synaptic vesicle protein modulator. J Clin Psychiatry 65:1162–1163
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 USA 101:9861–9866
Niespodziany I, Klitgaard H, Margineanu DG (2000) Levetiracetam: modulation of high voltage activated C++ current in CA1 pyramidal neurons of rat hippocampal slices (abstract). Epilepsia 41:37
Lukyanetz EA, Shkryl VM, Kostyuk PG (2002) Selective blockade of n-type calcium channels by levetiracetam. Epilepsia 43:9–18
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
Cardile V, Pavone A, Gulino R et al (2003) Expression of brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) in rat astrocyte cultures treated with levetiracetam. Brain Res 976:227–233
Hanon E, Klitgaard H (2001) Neuroprotective properties of the novel antiepileptic drug levetiracetam in the rat middle cerebral artery occlusion model of focal cerebral ischemia. Seizure 10:287–293
Wagner GL, Wilms EB, Van Donselaar GA et al (2003) Levetiracetam: preliminary experience in patients with primary brain tumours. Seizure 12:585–586
Newton HB, Goldlust SA, Pearl D (2006) Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. J Neurooncol 78:157–160
Maschio M, Albani F, Baruzzi A et al (2006) Levetiracetam therapy in patients with brain tumour and epilepsy. J Neurooncol 80:97–100
Alsaadi TM, Shatzel A, Marquez AV et al (2005) Clinical experience of levetiracetam monotherapy for adults with epilepsy: 1-year follow-up study. Seizure 14:139–142
Labate A, Colosimo E, Gambardella A et al (2006) Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an open label study. Seizure 15:214–218
Brodie MJ, Perucca E, Ryvlin P et al (2007) Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurol 68:402–408
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
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
Payakachat N, Summers KH, Barbuto JP (2006) A comparison of clinical practice guidelines in the initial pharmacological management of new-onset epilepsy in adults. J Manag Care Pharm 12:55–60
Glantz M, Recht LD (1997) Epilepsy in the cancer patient. In: Vecht CJ (ed) Handbook of Clinical Neurology. Elsevier Science, Amsterdam, pp 9–18
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
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
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Newton, H.B., Dalton, J., Goldlust, S. et al. Retrospective analysis of the efficacy and tolerability of levetiracetam in patients with metastatic brain tumors. J Neurooncol 84, 293–296 (2007). https://doi.org/10.1007/s11060-007-9373-8
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DOI: https://doi.org/10.1007/s11060-007-9373-8