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Levetiracetam monotherapy in patients with brain tumor-related epilepsy: seizure control, safety, and quality of life

  • Clinical Study – Patient Study
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Abstract

We performed a case series analysis to evaluate the effects of levetiracetam (LEV) monotherapy on seizures, adverse events, cognitive functioning and quality of life (QoL) in patients with brain tumor-related epilepsy (BTRE). We also explored the possible effects of systemic therapies on the efficacy of LEV. Twenty-nine patients were followed (13 female, 16 male; age 24–75 years) with 12 months of follow-up. Patients were evaluated by QoL and neuropsychological tests. At final follow-up, mean LEV dosage was 1991.4 mg/day. Among patients who reached the final follow-up of 12 months (n = 15), 1 patient had ≥50% reduction of seizure frequency (SF), and 14/15 were seizure free. The difference in presence/absence of seizures between baseline and final follow-up was significant (p < 0.001). Responder rate was 100%. We observed five side-effects: four mild (reversible) and one severe. Logistic regression revealed that chemotherapy and radiotherapy did not affect the efficacy of LEV in seizure outcome (p = 0.999). The following statistically significant observations emerged by tests’ evaluation: less worry about seizures, effects of antiepileptic, and ability to maintain social functions. Our data suggest that seizure occurrence can be an important warning sign that the clinician should heed throughout the duration of the illness. Patients with BTRE represent a unique patient population that presents difficulties regarding management of two very different pathologies: epilepsy on the one hand, and brain tumor on the other. Our data indicate that LEV, in patients with BTRE, is safe and efficacious, with positive impact on QoL.

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References

  1. Hildebrand J, Lecaille C, Perennes J, Delattre JY (2005) Epileptic seizures during follow-up of patients treated for primary brain tumors. Neurology 65:212–215

    Article  PubMed  Google Scholar 

  2. Maschio M, Dinapoli L, Vidiri A et al (2009) The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine. J Exp Clin Cancer Res 28:60

    Article  PubMed  Google Scholar 

  3. Maschio M, Dinapoli L, Saveriano F et al (2009) Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report. Acta Neurol Scand 120:210–212

    Article  PubMed  CAS  Google Scholar 

  4. Novy J, Stupp R, Rossetti AO (2009) Pregabalin in patients with primary brain tumors and seizures: a preliminary observation. Clin Neurol Neurosurg 111:171–173

    Article  PubMed  Google Scholar 

  5. Maschio M, Dinapoli L, Zarabla A et al (2008) Outcome and tolerability of topiramate in brain tumor associated epilepsy. J Neuro-Oncol 86:61–70

    Article  CAS  Google Scholar 

  6. Maschio M, Albani F, Baruzzi A et al (2006) Levetiracetam therapy in patients with brain tumour and epilepsy. J Neuro-Oncol 80:97–100

    Article  CAS  Google Scholar 

  7. Khan RB, Hunt DL, Thompson SJ (2004) Gabapentin to control seizures in children undergoing cancer treatment. J Child Neurol 19:97–101

    PubMed  Google Scholar 

  8. Striano S, Striano P, Boccella P, Noverino C, Bilo L (2002) Tiagabine in glial tumors. Epilepsy Res 49:81–85

    Article  PubMed  CAS  Google Scholar 

  9. Dinapoli L, Maschio M, Jandolo B, et al. (2009) Quality of life and seizure control in patients with brain tumor-related epilepsy treated with levetiracetam monotherapy: preliminary data of an open-label study. Neurol Sci May 5 [Epub ahead of print]

  10. Newton HB, Goldlust SA, Pearl D (2006) Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. J Neuro-Oncol 78:99–102

    Article  CAS  Google Scholar 

  11. Perucca E (2005) Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 61:246–255

    Article  Google Scholar 

  12. Vincenzi B, Snatini D, Grilli C, La Cesa A, Dianzani C, Tonini G (2004) Toxic epidermal necrolysis induced by oral phenobarbital and whole-brain radiotherapy in a breast cancer patient. J Clin Oncol 5:4649–4651

    Article  Google Scholar 

  13. Aguiar D, Pazo R, Duran I et al (2004) Toxic epidermal necrolysis in patients receiving anticonvulsants and cranial irradiation: a risk to consider. J Neuro-Oncol 66:345–350

    Article  Google Scholar 

  14. El Kamar FG, Posner JB (2004) Brain metastases. Semin Neurol 24:347–362

    Article  PubMed  Google Scholar 

  15. Wen PY, Marks PW (2002) Medical management of patients with brain tumors. Curr Opin Oncol 14:299–307

    Article  PubMed  Google Scholar 

  16. Eralp Y, Aydiner A, Tas F, Saip P, Topuz E (2001) Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation. Am J Clin Oncol 24:347–350

    Article  PubMed  CAS  Google Scholar 

  17. Glantz MJ, Cole BF, Forsyth PA et al (2000) Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neurology 54:1886–1893

    PubMed  CAS  Google Scholar 

  18. Micali G, Linthicum K, Han N, West D (1999) Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies. Pharmacotherapy 19:223–227

    Article  PubMed  CAS  Google Scholar 

  19. Mamon HJ, Wen P, Burns AC, Loeffler YS (1999) Allergic skin reactions to anticonvulsant medications in patients receiving cranial radiation therapy. Epilepsia 40:341–344

    Article  PubMed  CAS  Google Scholar 

  20. Oberndorfer S, Piribauer M, Marosi C, Lahrmann H, Hitzenberger P, Grisold W (2005) P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy. J Neuro-Oncol 72:255–260

    Article  CAS  Google Scholar 

  21. Vecht CJ, Van Breemen M (2006) Optimizing therapy of seizures in patients with brain tumours. Neurology 67(S4):S10–S13

    PubMed  Google Scholar 

  22. Soffietti R, Cornu P, Delattre JY et al (2006) EFNS guidelines on diagnosis and treatment of brain metastases: report of an EFNS task force. Eur J Neurol 13:674–681

    Article  PubMed  CAS  Google Scholar 

  23. Anderson GD (2004) Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs. Neurology 63(Suppl 4):S3–S8

    PubMed  CAS  Google Scholar 

  24. Hildebrand J (2004) Management of epileptic seizures. Curr Opin Oncol 16:314–317

    Article  PubMed  Google Scholar 

  25. Klein M, Engelberts NH, van der Ploeg HM et al (2003) Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life. Ann Neurol 54:514–520

    Article  PubMed  Google Scholar 

  26. Patsalos PN, Perucca E (2003) Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol 2:473–481

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  28. Chang SM, Kuhn JG, Robins HI (2001) A phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants. Cancer 91:417–422

    Article  PubMed  CAS  Google Scholar 

  29. Patsalos PN, Fröscher W, Pisani F, van Rijn CM (2002) The importance of drug interactions in epilepsy therapy. Epilepsia 43:365–385

    Article  PubMed  CAS  Google Scholar 

  30. French JA, Gidal BE (2000) Antiepileptic drugs interactions. Epilepsia 41(Suppl 8):S30–S36

    Article  PubMed  CAS  Google Scholar 

  31. Relling MV, Pui CH, Sandlund JT et al (2000) Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia. Lancet 356:285–290

    Article  PubMed  CAS  Google Scholar 

  32. 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 

  33. Lehmann DF, Hurteau TE, Newman N, Coyle TE (1997) Anticonvulsant usage is associated with an increased risk of procarbazine hypersensitivity reactions in patients with brain tumors. Clin Pharmacol Ther 62:225–229

    Article  PubMed  CAS  Google Scholar 

  34. Yap KY, Chui WK, Chan A (2008) Drug interactions between chemotherapeutic regimens and antiepileptics. Clin Ther 30:1385–1407

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. van Breemen MS, Wilms EB, Vecht CJ (2007) Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 6:421–430

    Article  PubMed  Google Scholar 

  37. Singh G, Rees JH, Sander JW (2007) Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment. J Neurol Neurosurg Psychiatry 78:342–349

    Article  PubMed  Google Scholar 

  38. Pace A, Vidiri A, Galiè E et al (2003) Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann Oncol 14:1722–1726

    Article  PubMed  CAS  Google Scholar 

  39. Ngo L, Nei M, Glass J (2006) Temozolomide treatment of refractory epilepsy in a patient with an oligodendroglioma. Epilepsia 47:1237–1238

    Article  PubMed  Google Scholar 

  40. Bosma I, Vos MJ, Heimans JJ et al (2007) The course of neurocognitive functioning in high-grade glioma patients. Neuro Oncol 9:53–62

    Article  PubMed  Google Scholar 

  41. Weitzner MA, Meyers CA (1997) Cognitive functioning and quality of life in malignant glioma patients: a review of the literature. Psycho-oncol 6:169–177

    Article  CAS  Google Scholar 

  42. Pignatti F, van den Bent M, Curran D et al (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084

    Google Scholar 

  43. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events v4.0, http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev4.pdf

  44. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

    PubMed  CAS  Google Scholar 

  45. Apolone G, Filiberti A, Cifani S, Ruggiata R, Mosconi P (1998) Evaluation of the EORTC QLQ-C30 questionnaire: a comparison with SF-36 Health Survey in a cohort of Italian long-survival cancer patients. Ann Oncol 9:549–557

    Article  PubMed  CAS  Google Scholar 

  46. Cramer JA, Van Hammèe G, N132 Study Group (2003) Maintenance of improvement in health-related quality of life during long-term treatment with levetiracetam. Epilepsy Behav 4:118–123

    Article  PubMed  Google Scholar 

  47. Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H (2004) Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology 62:23–27

    PubMed  CAS  Google Scholar 

  48. Brown PD, Buckner JC, O’Fallon JR et al (2003) Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the folstein mini-mental state examination. J Clin Oncol 21:2519–2524

    Article  PubMed  Google Scholar 

  49. Karnofsky DA, Burchenal JH, Armistead GC, Southam CM, Bernstein JL, Craver LF, Rhoads CP (1951) Triethylene melamine in the treatment of neoplastic disease. Arch Int Med 87:477–516

    CAS  Google Scholar 

  50. Mahoney FI, Barthel DW (1965) Functional evaluation: the Barthel Index. Md State Med J 14:61–65

    PubMed  CAS  Google Scholar 

  51. Meyers CA, Hess KR (2003) Multifaceted end points in brain tumor clinical trials: cognitive deterioration precedes MRI progression. Neuro-Oncol 5:89–95

    PubMed  Google Scholar 

  52. Rosati A, Tomassini A, Pollo B, Ambrosi C, Schwarz A, Padovani A, Sonetti B (2009) Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neuro-Oncol 93:395–400

    Article  Google Scholar 

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Acknowledgment

The authors wish to thank Ms Lesley Pritikin for reviewing the manuscript.

Funding source

This research was supported by UCB Pharma.

Disclosures

The authors have reported no conflicts of interest. The funding organization had no role in the design and conduct of the study, collection, management, analysis or interpretation of data.

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Authors and Affiliations

  1. Center for Tumor-Related Epilepsy, Neurology Unit, Department of Neuroscience and Cervical-Facial Pathology, National Institute for Cancer ‘Regina Elena’, Via Elio Chianesi 53, 00144, Rome, Italy

    Marta Maschio & Loredana Dinapoli

  2. S.C. Epidemiology, National Institute for Cancer ‘Regina Elena’, Via Elio Chianesi 53, 00144, Rome, Italy

    Francesca Sperati

  3. Neurology Unit, Department of Neuroscience and Cervical-Facial Pathology, National Institute for Cancer ‘Regina Elena’, Via Elio Chianesi 53, 00144, Rome, Italy

    Andrea Pace

  4. Department of Oncology, National Institute for Cancer ‘Regina Elena’, Via Elio Chianesi 53, 00144, Rome, Italy

    Alessandra Fabi

  5. Department of Radiology, National Institute for Cancer ‘Regina Elena’, Via Elio Chianesi 53, 00144, Rome, Italy

    Antonello Vidiri

  6. Scientific Direction, National Institute for Cancer ‘Regina Elena’, Via Elio Chianesi 53, 00144, Rome, Italy

    Paola Muti

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  1. Marta Maschio
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  2. Loredana Dinapoli
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Correspondence to Marta Maschio.

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Maschio, M., Dinapoli, L., Sperati, F. et al. Levetiracetam monotherapy in patients with brain tumor-related epilepsy: seizure control, safety, and quality of life. J Neurooncol 104, 205–214 (2011). https://doi.org/10.1007/s11060-010-0460-x

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  • DOI: https://doi.org/10.1007/s11060-010-0460-x

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