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Seizure response to perampanel in drug-resistant epilepsy with gliomas: early observations

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Abstract

Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a shared mechanism of AMPA-activation involving both seizure activity and tumor growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE in low- and high-grade gliomas. Seizure response was defined as 50% drop in seizure frequency or as seizure-freedom. Cognitive function was examined by computerized test on cognitive speed (CTCS), which is sensitive to the type of cognitive dysfunction associated with epilepsy and use of anticonvulsants. Treatment policy included reduction of dose or discontinuation of one or more concurrent AEDs, once a seizure-free response was observed. Twelve patients were included patients, median age 41 years, 9 men versus 3 women and 6 months median duration of follow-up. An objective seizure response (75%) was observed in 9 (75%) out of 12 patients: 50%-seizure response in 3, seizure-freedom in 6, which is plainly more than seen with other types of DRE. Side-effects occurred in six patients. Cognitive function as examined by CTCS improved in six out of eight associated withlowering of concurrent AEDs. The final median dose of PER was 8 mg (varying between 2 and 12 mg). These results of an objective seizure response in 9 (75%) out of 12 patients treated by PER in DRE may be interpreted as a surrogate-marker of tumor response secondary to AMPA blockade, advancing confirmation by MR imaging. These results warrant further study of PER on tumor activity in gliomas.

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References

  1. van Breemen MSM, Rijsman RM, Taphoorn MJB, Walchenbach R, Zwinkels H, Vecht CJ (2009) Efficacy of anti-epileptic drugs in patients with gliomas and seizures. J Neurol 256(9):1519–1526

    Article  PubMed  Google Scholar 

  2. Pallud J, Audureau E, Blonski M, Sanai N, Bauchet L, Fontaine D et al (2014) Epileptic seizures in diffuse low-grade gliomas in adults. Brain 137:449–462

    Article  PubMed  Google Scholar 

  3. Kerkhof M, Dielemans JCM, van Breemen MS, Zwinkels H, Walchenbach R, Taphoorn MJ et al (2013) Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro-Oncology 15(7):961–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Toledo M, Sarria-Estrada S, Quintana M, Maldonado X, Martinez-Ricarte F, Rodon J et al (2015) Prognostic implications of epilepsy in glioblastomas. Clin Neurol Neurosurg 139:166–171

    Article  PubMed  Google Scholar 

  5. de Groot J, Sontheimer H (2011) Glutamate and the biology of gliomas. Glia 59(8):1181–1189

    Article  PubMed  Google Scholar 

  6. Robel S, Sontheimer H (2016) Glia as drivers of abnormal neuronal activity. Nat Neurosci 19(1):28–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Huberfeld G, Vecht CJ (2016) Seizures and gliomas - towards a single therapeutic approach. Nat Rev Neurol 12(4):204–216

    Article  PubMed  Google Scholar 

  8. Grossman SA, Ye X, Chamberlain M, Mikkelsen T, Batchelor T, Desideri S et al (2009) Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol 27(25):4155–4161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Froklage FE, Oosterbaan LJ, Sizoo EM, de Groot M, Bosma I, Sanchez E et al (2014) Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study. J Neurooncol 116(2):387–394

    Article  CAS  PubMed  Google Scholar 

  10. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G et al (2010) Definition of drug resistant epilepsy. Consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies. Epilepsia 51(9):1069

    CAS  PubMed  Google Scholar 

  11. Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A et al (2013) Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia 54(8):1481–1489

    Article  CAS  PubMed  Google Scholar 

  12. Lutz MT, Helmstaedter C (2005) EpiTrack: tracking cognitive side effects of medication on attention and executive functions in patients with epilepsy. Epilepsy Behav 7(4):708–714

    Article  CAS  PubMed  Google Scholar 

  13. Taylor J, Kolamunnage-Dona R, Marson AG, Smith PEM, Aldenkamp AP, Baker GA et al (2010) Patients with epilepsy: cognitively compromised before the start of antiepileptic drug treatment? Epilepsia 51(1):48–56

    Article  PubMed  Google Scholar 

  14. Durand T, Bernier M-O, Leger I, Taillia H, Noel G, Psimaras D et al (2015) Cognitive outcome after radiotherapy in brain tumor. Curr Opin Oncol 27(6):510–515

    Article  CAS  PubMed  Google Scholar 

  15. Taillia H, Bompaire F, Jacob J, Noel G (2013) Cognitive evaluation during brain radiotherapy in adults: a simple assessment is possible. Cancer Radiother 17(5–6):413–418

    Article  CAS  PubMed  Google Scholar 

  16. Chang EF, Potts MB, Keles GE, Lamborn KR, Chang SM, Barbaro NM et al (2008) Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 108(2):227–235

    Article  PubMed  Google Scholar 

  17. Chaichana KL, Parker SL, Olivi A, Quinones-Hinojosa A (2009) Long-term seizure outcomes in adult patients undergoing primary resection of malignant brain astrocytomas clinical article. J Neurosurg 111(2):282–292

    Article  PubMed  Google Scholar 

  18. Mirsattari SM, Chong JJR, Hammond RR, Megyesi JF, Macdonald DR, Lee DH et al (2011) Do epileptic seizures predict outcome in patients with oligodendroglioma? Epilepsy Res 94(1–2):39–44

    Article  PubMed  Google Scholar 

  19. French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A et al (2012) Adjunctive perampanel for refractory partial-onset seizures randomized phase III study 304. Neurology 79(6):589–596

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kramer LD, Satlin A, Krauss GL, French J, Perucca E, Ben-Menachem E et al (2014) Perampanel for adjunctive treatment of partial- onset seizures: a pooled dose- response analysis of phase III studies. Epilepsia 55(3):423–431

    Article  PubMed  Google Scholar 

  21. Montouris G, Yang H, Williams B, Zhou S, Laurenza A, Fain R (2015) Efficacy and safety of perampanel in patients with drug-resistant partial seizures after conversion from double-blind placebo to open-label perampanel. Epilepsy Res 114:131–140

    Article  CAS  PubMed  Google Scholar 

  22. Besag FMC, Patsalos PN (2016) Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures. Neuropsychiatr Dis Treat 12:1215–1220

    PubMed  PubMed Central  Google Scholar 

  23. Klein M, Engelberts NHJ, van der Ploeg HM, Trenite D, Aaronson NK, Taphoorn MJB et al (2003) Epilepsy in low-grade gliomas: The impact on cognitive function and quality of life. Ann Neurol 54(4):514–520

    Article  PubMed  Google Scholar 

  24. Bosma I, Vos MJ, Heimans JJ, Taphoorn MJ, Aaronson NK, Postma TJ et al (2007) The course of neurocognitive functioning in high-grade glioma patients. Neuro Oncol 9(1):53–62

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mecarelli O, Vicenzini E, Pulitano P, Vanacore N, Romolo FS (2004) Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. Ann Pharmacother 38(11):1816–1822

    Article  CAS  PubMed  Google Scholar 

  26. Taylor J, Baker GA (2010) Newly diagnosed epilepsy: Cognitive outcome at 5 years. Epilepsy Behav 18(4):397–403

    Article  PubMed  Google Scholar 

  27. Ruet A, Deloire MSA, Charre-Morin J, Hamel D, Brochet B (2013) A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis. Mult Scler J 19(12):1665–1672

    Article  Google Scholar 

  28. Englot DJ, Berger MS, Barbaro NM, Chang EF (2011) Predictors of seizure freedom after resection of supratentorial low-grade gliomas a review. J Neurosurg 115(2):240–244

    Article  PubMed  Google Scholar 

  29. Ruda R, Magliola U, Bertero L, Trevisan E, Bosa C, Mantovani C et al (2013) Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study. Neuro-Oncology 15(12):1739–1749

    Article  PubMed  PubMed Central  Google Scholar 

  30. Koekkoek JAF, Dirven L, Heimans JJ, Postma TJ, Vos MJ, Reijneveld JC et al (2016) Seizure reduction is a prognostic marker in low-grade glioma patients treated with temozolomide. J Neurooncol 126(2):347–354

    Article  CAS  PubMed  Google Scholar 

  31. Vecht CJ, Kerkhof M, Duran-Pena A (2014) Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist 19(7):751–759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Roelcke U, Wyss MT, Nowosielski M, Ruda R, Roth P, Hofer S et al (2016) Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas. Neuro-Oncology 18(5):744–751

    Article  PubMed  Google Scholar 

  33. Benit C, Vecht C (2016) Seizures and cancer: drug Interactions of anticonvulsants with chemotherapeutic agents, tyrosine-kinase inhibitors and glucocorticoids. Neuro-oncol Pract 3(4):245–260

    Article  Google Scholar 

  34. Gidal BE, Laurenza A, Hussein Z, Yang H, Fain R, Edelstein J et al (2015) Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with epilepsy. Neurology 84(19):1972–1980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T et al (2007) Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation. J Neurosci 27(30):7987–8001

    Article  CAS  PubMed  Google Scholar 

  36. De Groot JF, Piao Y, Lu L, Fuller GN, Yung WKA (2008) Knockdown of GluR1 expression by RNA interference inhibits glioma proliferation. J Neurooncol 88(2):121–133

    Article  PubMed  Google Scholar 

  37. Luksch H, Uckermann O, Stepulak A, Hendruschk S, Marzahn J, Bastian S et al (2011) Silencing of selected glutamate receptor subunits modulates cancer growth. Anticancer Res 31(10):3181–3192

    CAS  PubMed  Google Scholar 

  38. Choi J, Stradmann-Bellinghausen B, Yakubov E, Savaskan NE, Regnier-Vigouroux A (2015) Glioblastoma cells induce differential glutamatergic gene expressions in human tumor-associated microglia/macrophages and monocyte-derived macrophages. Cancer Biol Ther 16(8):1205–1213

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

No funding has supported this research. GH has received consulting fees from Eisai Ltd.

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Authors and Affiliations

  1. Department of Neurology Mazarin, Université Pierre et Marie Curie, INSERM U1129, 75015, Paris, France

    Charles Vecht, Alberto Duran-Peña, Caroline Houillier & Thomas Durand

  2. Neurosurgery Babinski, Université Pierre et Marie Curie, INSERM U1129, 75015, Paris, France

    Laurent Capelle

  3. Pitié-Salpêtrière Hospital, and Laboratory of Neurophysiology, Université Pierre et Marie Curie, INSERM U1129, 75015, Paris, France

    Gilles Huberfeld

  4. Service Neurologie Mazarin, CHU Pitié-Salpêtrière, Paris, 47 Bld. de l´Hopital, 75651, PARIS CEDEX 13, France

    Charles Vecht

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  1. Charles Vecht
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  2. Alberto Duran-Peña
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  4. Thomas Durand
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  5. Laurent Capelle
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Correspondence to Charles Vecht.

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Vecht, C., Duran-Peña, A., Houillier, C. et al. Seizure response to perampanel in drug-resistant epilepsy with gliomas: early observations. J Neurooncol 133, 603–607 (2017). https://doi.org/10.1007/s11060-017-2473-1

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  • DOI: https://doi.org/10.1007/s11060-017-2473-1

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