Anticonvulsant therapy in brain-tumor related epilepsy


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VOLUME 24 , ISSUE 1 (June 2016) > List of articles

Anticonvulsant therapy in brain-tumor related epilepsy

Walter Fröscher * / Timo Kirschstein / Johannes Rösche

Keywords : brain-tumor, epilepsy, antiepileptic drugs, chemiotherapeutic drugs, pharmacokinetic interactions

Citation Information : Journal of Epileptology. Volume 24, Issue 1, Pages 41-56, DOI:

License : (CC BY 4.0)

Received Date : 06-February-2016 / Accepted: 29-March-2016 / Published Online: 06-April-2016



Background. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10–100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.

Aim. This review addresses the special aspects of antiepileptic drug (AED) therapy in brain tumor-related epilepsy.

Methods. We analyzed the literature up to December 2015.

Results. Based on current evidence the management of tumor-related seizures does not differ substantially from that applied to epilepsies from other etiologies. Therefore, the choice of an AED is based, above all, on tolerability and pharmacokinetic interactions with chemotherapeutic drugs. Levetiracetam is recommended by many authors as first-line therapy in brain tumor-related epilepsy. Due to the possibility of interactions, the combination of enzyme-inducing AEDs and chemotherapeutic drugs, is usually not recommended as a first choice. Currently there is no evidence that prophylactic prescription of long-term AEDs in brain tumor-patients who did not present with seizures is justified. Because of the high risk of recurrence, however, AED treatment should be strongly considered after a single brain tumor-related seizure. The decision to withdraw AEDs must carefully consider the risk of seizure recurrence.

Conclusion. At present levetiracetam is the preferred drug in brain tumor-related epilepsy, especially when drug interactions need to be avoided. In the future we hope to acquire more targeted drugs against this disorder by uncovering its pathogenesis.

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Avila E.K., Graber J.: Seizures and epilepsy in cancer patients. Curr. Neurol. Neurosci. Rep., 2010, 10: 60–67.


Bain E., Birhiray R.E., Reeves D.: Drug-drug interaction between methotrexate and levetiracetam resulting in delayed methotrexate elimination. Ann. Pharmacother., 2014, 48: 292–296.


Bauer R., Ortler M., Seiz-Rosenhagen M. et al.: Treatment of epileptic seizures in brain tumors: a critical review. Neurosurg. Rev., 2014, 37: 381–388.


Baxter K., Preston C.L. (eds): Stockley’s Drug Interactions. 10th ed., Pharmaceutical Press, London–Chicago 2013.


Berg A.T., Berkovic S.F., Brodie M.J., Buchhalter J., Cross J.H., van Emde Boas W. et al.: Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE commission on classification and terminology, 2005–2009. Epilepsia, 2010, 51: 676–685.


Blumcke I.: Epilepsy-associated brain tumors. In: H. Stefan and W.H. Theodore (eds), Handbook of clinical neurology. Epilepsy. part II. 3rd series, Elsevier, Amsterdam 2012, vol. 108: 559–568.


Bobustuc G.C., Baker C.H., Limaye A., Jenkins W.D., Pearl G., Avgeropoulos N.G. et al.: Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomide. Neuro-Oncol., 2010, 12: 917–927.


Boehling N.S., Sulman E.P.: Outcomes of patients with glioblastoma receiving concurrent radiation treatment and antiepileptic agents with histone deacetylase inhibitor activity. Cancer Network (, April 30, 2015.


Boehmerle W., Huehnchen P., Endres M.: Neurologische Nebenwirkungen von Zytostatika. Akt. Neurol., 2014, 41: 21–34.


Bourg V., Lebrun C., Chichmanian R.M., Thomas P., Frenay M.: Nitrosurea-cisplatin based chemotherapy associated with valproate: increase of haematologic toxicity. Ann. Oncol., 2001, 12: 217–219.


Brackenbury W.J., Nelson M., Yang M., Dowle A.A., Thomas J.R. et al.: Targeting voltage-gated sodium channels with the antiepileptic drug phenytoin inhibits breast tumor growth and metastasis. Cancer Res., 2015, 75 (9 Suppl. S), P6-03-10.


Brogna Ch, Robles G., Duffau H.: Brain tumors and epilepsy. Expert Rev. Neurother., 2008, 8: 941–955.


Bruna J., Miro J., Roser V.: Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment. Expert Rev. Clin. Pharmacol., 2013, 6: 333–344.


Buckingham S.C., Campbell S.L., Haas B.R., Montana V., Robel St., Ogunrinu T. et al.: Glutamate release by primary brain tumors induces epileptic activity. Nat. Med., 2011, 17: 1269–1274.


Činčarova L., Zdrahal Z., Fajkus J.: New perspectives of valproic acid in clinical practice. Expert Opin. Investig. Drugs, 2013, 22: 1435–1447.


Cotterman-Hart S.: Antiepileptic drugs: First generation. In: H.B. Newton and M. Maschio (eds), Epilepsy and brain tumors. Elsevier, Amsterdam 2015, 159–169.


Das R.R., Artsy E., Hurwitz S., Wen P.Y., Black P., Golby A. et al.: Outcomes after discontinuation of antiepileptic drugs after surgery in patients with low grade brain tumors and meningiomas. J. Neurooncol., 2012, 107: 565–570.


De Curtis M., Librizzi L., Avanzini G.: Mechanisms of focal epileptogenesis. In: H.B. Newton and M. Maschio (eds), Epilepsy and brain tumors. Elsevier, Amsterdam 2015, 101–109.


De Groot M., Reijneveld J.C., Aronica E., Heimans J.J.: Epilepsy in patients with a brain tumor: focal epilepsy requires forced treatment. Brain, 2012, 135: 1002–1016.


de Oliveira J.A., Santana I.A., Caires I.Q.S., Caires-Lima R., Miranda V.C., Protasio B.M. et al.: Antiepileptic drug prophylaxis in primary brain tumor patients: is current practice in agreement to the consensus? J. Neurooncol., 2014, 120: 399–403.


Diener H.C., Weimar C., Berlit P., Deuschl G., Elger C., Gold R. et al. (eds.): Leitlinien für Diagnostik und Therapie in der Neurologie. Kap. 76, Gliome. 5. Aufl., Thieme, Stuttgart, 2012, 922–938.


Englot D.J., Magill S.T., Han S.J., Chang E.F., Berger M.S., Mc- Dermott M.W.: Seizures in supratentorial meningioma: a systematic review and meta-analysis. J. Neurosurg., 2015, 4: 1–10.


Froscher W.: Drug resistant epilepsy. Epileptologia, 2012, 20: 17–23.


Froscher W., Kirschstein T., Rosche J.: Antiepileptikabehandlung bei Hirntumor-bedingten epileptischen Anfällen (Anticonvulsant therapy for brain tumor-related epilepsy). Fortschr. Neurol. Psychiat., 2014, 82: 678–690.


Gefroh-Grimes H.A., Gidal B.E.: Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics. Acta Neurol. Scand., 2016, 133: 4–16.


Gerstner T., Teich M., Bell N., Longin E., Dempfle C.-E., Brand J. et al.: Valproate-associated coagulopathies are frequent and variable in children. Epilepsia, 2006, 47: 1136–1143.


Glantz M.J., Cole B.F., Forsyth P.A., Recht L.D., Wen P.Y., Chamberlain M.C. et al.: Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neurology, 2000, 54: 1886–1893.


Glauser T., Ben-Menachem E., Bourgeois B., Caan A.A., Guerreiro C., Kalviainen R. et al.: Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2013, 54: 551–563.


Goldlust S.A., Hsu M., Lassman A.B., Panageas K.S., Avila E.K.: Seizure prophylaxis and melanoma brain metastases. J. Neurooncol., 2012; 108: 109–114.


Goonawardena J., Marshman L.A., Drummond K.J.: Brain tumor-associated status epilepticus. J. Clin. Neurosci., 2015, 22: 29–34.


Grenader T., Gipps M., Shavit L., Gabizon A.: Significant drug interaction: Phenytoin toxicity due to erlotinib. Lung cancer, 2007, 57: 404–406.


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


Guerrini R., Rosati A., Giordano F., Genitori L., Barbara C.: The medical and surgical treatment of tumoral seizures: Current and future perspectives. Epilepsia, 2013, 54 (Suppl. 9): 84–90.


Guthrie G.D., Eljamel S.: Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme. J. Neurosurg., 2013, 118: 859–865.


Hall W.A., Djalilian H.R., Nussbaum E.S., Cho K.H.: Longterm survival with metastatic cancer to the brain. Med. Oncol., 2000, 17: 279–286.


Happold C., Gorlia T., Chinot O., Gilbert M., Nabors B., Wick W. et al.: Does valproic acid improve survival in glioblastoma? A meta-analysis of randomized trials in newly diagnosed glioblastoma. Neuro-Oncology, 2015, 17: v10–v17. doi:10.1093/neuonc/nov205.10.


Hemmer R.: Die Verkennung der Hirntumoren infolge psychischer Veränderungen. Dtsch. Med. Wschr., 1956, 81: 1305– 1308.


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


Hu A., Xu Z., Kim R.Y., Nguyen A., Lee J.W., Kesari S.: Seizure control: A secondary benefit of chemotherapeutic temozolomide in brain cancer patients. Epilepsy Res., 2011, 95: 270–272.


Ikeda H., Murakami T., Takano M., Usui T., Kihira K.: Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient. Br. J. Clin. Pharmacol., 2005, 59: 593–597.


Iwamoto F.M., Kreisl T.N., Kim L., Duic J.P., Butman J.A., Albert P.S. et al.: Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas. Cancer, 2010, 116: 1776–1782.


Jaeckle K.A., Ballman K., Furth A., Buckner J.C.: Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma. Neurology, 2009, 73: 1207–1213.


Japp A., Gielen G.H., Becker A.J.: Recent aspects of classification and epidemiology of epilepsy-associated tumors. Epilepsia, 2013, 54 (Suppl. 9): 5–11.


Jongeling A.C., Canoll P.D., Schevon C., Srinivasan S.: Seizure outcomes after glioma resection. Epilepsy Currents. Conference: 68th Annual Meeting of the American Epilepsy Society, AES 2014 Seattle, WA United States. Conference Publication: 15 (pp 503–504), 2015.


Kerkhof M., Dielemans J.C., van Breemen M.S., Zwinkels H., Walchenbach R., Taphoorn M. et al.: Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro-Oncol., 2013, 15: 961–967.


Kerkhof M. and Vecht Ch.J.: Seizure characteristics and prognostic factors of gliomas. Epilepsia, 2013, 54 (Suppl. 9): 12–17.


Kerrigan S.: Drug treatment of epilepsy in people with brain tumors. Eur. J. Oncol., 2010, 4: 9–10.


Khan R.B. and Omar A.: Seizure recurrence and risk factors after antiepileptic drug withdrawal in children with brain tumors. Epilepsia, 2006, 47: 375–379.


Kim L.G., Johnson T.L., Marson A.G., Chadwick D.W.: Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial. Lancet Neurol., 2006, 5: 317–322.


Kim Y.H., Kim T., Joo J.D., Han J.H., Kim Y.J., Yun C.H. et al.: Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme. Cancer, 2015, 121: 2926–2932.


Kirschstein T., Kohling R.: Animal models of tumor-associated epilepsy. J. Neurosci. Methods, 2015, Jun 16. pii: S0165- 0270(15)00225-3. doi: 10.1016/j.jneumeth.2015.06.008. [Epub ahead of print].


Koekkoek J.A.F., Dirven L., Heimans J.J., Postma T.J., Vos M.J., Reijneveld J.C. et al.: Seizure reduction in a low-grade glioma: More than a beneficial side effect of temozolomide. J. Neurol. Neurosurg. Psychiatry, 2015, 6: 366–373.


Kong X., Guan J., Yang Y., Li Y., Ma W., Wang R.: A metaanalysis: Do prophylactic antiepileptic drugs in patients with brain tumors decrease the incidence of seizures? Clin. Neurol. Neurosurg., 2015, 134: 98–103.


Kramer G.: Tumorbedingte epileptische Anfälle bei Erwachsenen. Epilepsieblätter, 1999, 12: 2–6.


Krumholz A., Wiebe S., Gronseth, G.S., Gloss D.S., Sanchez A.M., Kabir A.A. et al.: Evidence-based guideline: Management of an unprovoked first seizure in adults. Neurology, 2015, 84: 1705–1713.


Liigant A., Haldre S., Oun A., Linnamagi U., Saar A., Asser T. et al.: Seizure disorders in patients with brain tumors. Europ. Neurol., 2001, 45: 46–51.


Liubinas S.V., O’Brien T.J., Moffat B.M., Drummond K.J., Morokoff A.P., Kaye A.H.: Tumor associated epilepsy and glutamate excitotoxicity in patients with gliomas. J. Clin. Neurosci., 2014, 21: 899–908.


Lopez J.: Brain-tumor-related epilepsy in children. In: H.B. Newton and M. Maschio (eds.), Epilepsy and brain tumors. Elsevier, Amsterdam 2015, 65–99.


Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A. et al.: The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol., 2007, 114: 97–109.


Luyken C., Blumcke I., Fimmers R. Urbach H., Elger C.E., Wiestler O.D. et al.: The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects. Epilepsia, 2003, 44: 822–830.


Lynam L.M., Lyons M.K., Drazkowski J.F., Sirven J.I., Noe K.H., Zimmerman R.S. et al.: Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin. Neurol. Neurosurg., 2007, 109: 634–638.


Mamon H.J., Wen P.Y., Burns A.C., Loeffler J.S.: Allergic skin reactions to anticonvulsant medications in patients receiving cranial radiation therapy. Epilepsia, 1999, 40: 341–344.


Maschio M.: Brain tumor-related epilepsy. Curr. Neuropharmacol., 2012, 10: 124–133.


Maschio M., Dinapoli L., Sperati F., Fabi A., Pace A., Vidiri A. et al.: Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy. Open-label pilot study for assessing the efficacy, tolerability and impact on quality of life. J. Neuro-Oncol., 2012, 106: 651–656.


Maschio M., Newton H.B.: Brain tumor-related epilepsy: Introduction and overview. In: H.B. Newton and M. Maschio (eds.), Epilepsy and brain tumors. Elsevier, Amsterdam 2015a, 1–9.


Maschio M., Newton H.B.: Clinical approach to brain tumorrelated epilepsy. In: H.B. Newton and M. Maschio (eds.), Epilepsy and brain tumors. Elsevier, Amsterdam etc., 2015b, 207–223.


Meyer A., Froscher W.: Anfallssteigernde Medikamente und Drogen. In: W. Fröscher, F. Vassella, A. Hufnagel (eds.), Die Epilepsien. 2. Aufl., Schattauer, Stuttgart–New York 2004, 523–541.


Moots P., Marciunas R., Eisert D., Parker R.A., Laporte K., Abou-Khalil B.: The course of seizure disorders in patients with malignant gliomas. Arch. Neurol., 1995, 52: 717–724.


Motl S., Zhuang Y., Waters Ch. M., Clinton St.: Pharmacokinetic considerations on the treatment of CNS tumors. Clin. Pharmacokinet., 2006, 45: 871–903.


Neher K.-D.: Interaktionen: Beeinflussung der Serumkonzentration von Antiepileptika durch andere Medikamente. In: Fröscher W., Blankenhorn V., May Th. W., Neher K.-D., Rambeck B., Steinhoff B.J.: Pharmakotherapie der Epilepsien. 4. Aufl., Schattauer, Stuttgart–New York, 2008a, 135–177.


Neher K.-D. Interaktionen: Beeinflussung der Serumkonzentration von Nicht-Antiepileptika durch Antiepileptika. In: W. Fröscher, V. Blankenhorn, Th.W. May, K.-D. Neher, B. Rambeck, B.J. Steinhoff: Pharmakotherapie der Epilepsien. 4. Aufl., Schattauer, Stuttgart–New York, 2008b, 178–196.


Newton H.B., Ray L.: Supportive care of brain tumor patients. In: H.B. Newton and M. Maschio (eds), Epilepsy and brain tumors. Elsevier, Amsterdam 2015, 45–63.


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


Pallud J., Capelle L., Haberfeld G.: Tumoral epileptogenicity: how does it happen? Epilepsia, 2013, 54 (Suppl. 9): 30–34.


Patsalos P.N.: Drug interactions with the newer antiepileptic drugs (AEDs) – Part 2: Pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders. Clin. Pharmacokinet., 2013, 52: 1045–1061.


Paulus W., Hasselblatt M.: Tumoren. In: G. Klöppel, H.H. Kreipe, W. Remmele (eds.), Pathologie, Bd. Neuropathologie. 3. Aufl. Springer, Berlin–Heidelberg, 2012, 481–549.


Perucca E.: Optimizing antiepileptic drug treatment in tumoral epilepsy. Epilepsia, 2013, 54 (Suppl. 9): 97–104.


Piotrowski A.F., Blakeley J.: Clinical management of seizures in patients with low-grade glioma. Semin. Radiat. Oncol., 2015, 25: 219–224.


Plotkin S.R., Wen P.Y.: Neurologic complications of cancer therapy. Neurol. Clin., 2003, 21: 279–318.


Prayson R.A.: Brain tumors in adults with medically intractable epilepsy. Am. J. Clin. Pathol., 2011, 136: 557–563.


Pruitt A.A.: Medical management of patients with brain tumors. Curr. Treat. Options Neurol., 2011, 13: 413–426.


Radhakrishnan A., Abraham M., Vilanilam G., Menon R., Menon D., Kumar H. et al.: Surgery for “Long-term epilepsy associated tumors (LEATs)”: Seizure outcome and its predictors. Clin. Neurol. Neurosurg., 2016, 141: 98–105


Rambeck B. and May Th.W.: Enzyminduktion in der Leber durch Antiepileptika. In: W. Fröscher, V. Blankenhorn, Th.W. May, K.-D. Neher, B. Rambeck, B.J. Steinhoff: Pharmakotherapie der Epilepsien. 4. Aufl., Schattauer, Stuttgart–New York 2008, 128–130.


Ray L., Maschio M., Newton H.B.: Antiepileptic drugs and brain tumor patients. In: H.B. Newton and M. Maschio (eds), Epilepsy and brain tumors. Elsevier, Amsterdam 2015, 195–205.


Reddy J.P., Dawood S., Mitchell M., Debeb B.G., Bloom E., Gonzales-Anqulo A.M. et al.: Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy. Radiother. Oncol., 2015, 117: 308–314.


Reif P.S., Strik H., Rosenow F.: Therapeutisches Management bei Patienten mit tumorassoziierter Epilepsie – Pharmakotherapie. Z. Epileptol., 2012, 25: 104–113.


Relling M.V., Pui C.-H., Sandlund J.T., Rivera G.K., Hancock M.L., Boyett J.M. et al.: Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia. Lancet, 2000, 356: 285–290.


Rosche J., Piek J., Hildebrandt G., Grossmann A., Kirschstein T., Benecke R.: Perampanel in the treatment of a patient with glioblastoma multiforme without IDH 1 mutation and without MGMT promotor methylation. Fortschr. Neurol. Psychiat., 2015, 83: 286–289.


Rogers L.R.: Chemotherapy and immunotherapy of brain tumors: What the epileptologist must know. Epilepsia, 2013, 54 (Suppl. 9): 105–108.


Rossetti A.O., Stupp R.: Epilepsy in brain tumor patients. Curr. Opin. Neurol., 2010, 23: 603–609.


Ruda R., Bello L., Duffau H., Soffietti R.: Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro-Oncol., 2012, 14: 55–64.


Ruda R., Trevisan E., Sofietti R.: Epilepsy and brain tumors. Curr. Opin. Oncol., 2010, 22: 611–620.


Ruggiero A., Rizzo D., Mastrangelo St., Battaglia D., Attina G., Riccardi R. et al.: Interactions between antiepileptic and chemotherapeutic drugs in children with brain tumors: Is it time to change treatment? Pediatr. Blood Cancer, 2010, 54: 193–198.


Salmaggi A., Granata T., Rigamonti A.: Pathophysiology of brain tumor-related epilepsy. In: H.B. Newton and M. Maschio (eds.), Epilepsy and brain tumors. Elsevier, Amsterdam 2015, 111–118.


Sayegh E.T., Fakurnejad S., Oh T., Bloch O., Parsa A.T.: Anticonvulsant prophylaxis for brain tumor surgery: determining the current best available evidence. J. Neurosurg., 2014, 121: 1139–1147.


Schiff D., Lee E.Q., Nayak L., Norden A.D., Reardon D.A., Wen P.: Medical management of brain tumors and the sequelae of treatment. Neuro-Oncol., 2015, 17: 488–504.


Schmidt D., Loscher W.: Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: a review of current clinical experience. Acta Neurol. Scand., 2005, 111: 291–300.


Seeck M.: Surgical treatment of tumoral temporal-lobe epilepsy. Lancet Neurol., 2003, 2: 722–723.


Sherman J.H., Moldovan K., Yeoh H.K., Starke R.M., Pouratian N., Shaffrey M.E. et al.: Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J. Neurosurg., 2011, 114: 1617–1621.


Sirven J.I., Wingerchuk D.M., Drazkowski J.F., Lyons M.K., Zimmerman R.S.: Seizure prophylaxis in patients with brain tumors: A meta-analysis. Mayo Clin. Proc., 2004, 79: 1489–1494.


Spitzer M.: Chemo-Gehirn – Nebenwirkungen von Chemotherapie in Erleben, Denken, Fühlen und Handeln. Nervenheilkunde, 2014, 33: 319–324.


Stefan H.: Hirntumoren und Epilepsien. Z. Epileptol., 2009, 22: 65–71.


Stupp R., Mason, W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J. et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med., 2005, 352: 987–996.


Stupp R., Wong E.T., Kanner A.A., Steinberg D., Engelhard H., Heidecke V. et al.: NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality. Eur. J. Cancer., 2012, 48: 2192–2202.


Stupp R., Wong E., Scott Ch., Taillibert S., Kanner A., Kesari S. et al.: Interim analysis of the EF-14 trial: A prospective, multi-center trial of NovoTTF-100A together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM. Neuro-Oncol., 2014, 16 (Suppl. 5): v1. Doi: 10.1093/neuronc/nou265.40.


Swisher Ch.B., Doreswamy M., Gingrich K.J., Vredenburgh J.J., Kolls B.J.: Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocrit. Care, 2012, 16: 109–113.


Tanaka H., Jotoku H., Takasaki M., Ibayashi Y., Watanabe K., Takahashi M.: Effect of capecitabine therapy on the blood levels of antiepileptic drugs – report of two cases. Gan To Kagaku Ryoho., 2014, 41: 527–530.


Tandon N. and Esquenazi Y.: Resection strategies in tumoral epilepsy: Is a lesionectomy enough? Epilepsia, 2013, 54 (Suppl. 9): 72–78.


Tibussek D., Distelmaier F., Schonberger S., Gobel U., Mayatepek E.: Antiepileptic treatment in paediatric oncology – an interdisciplinary challenge. Klin. Pädiatr., 2006, 218: 340–349.


Tinchon A., Oberndorfer S., Marosi C., Gleiss A., Geroldinger A., Sax C.: Haematological toxicity of valproic acid compared to levetiracetam in patients with glioblastoma multiforme undergoing concomitant radiochemotherapy: a retrospective cohort study. J. Neurol., 2015, 262: 179–186.


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


Van Breemen M.S.M., Wilms E.B., Vecht Ch. J.: Epilepsy in patients with brain tumors: epidemiology, mechanism and management. Lancet Neurol., 2007, 6: 421–430.


Van Breemen M.S.M., Wilms E.B., Vecht C.J.: Seizure control in brain tumors. In: W. Grisold and R. Soffietti (eds.), Handbook of clinical neurology. Neuro-oncology. Elsevier, Amsterdam 2012, vol. 104 (3rd series), 381–389.


Van Breemen M.S.M., Rijsman R.M., Taphoorn M.J.B., Walchenbach R., Zwinkels H., Vecht J.C.: Efficacy of anti-epileptic drugs in patients with gliomas and seizures. J. Neurol., 2009, 256: 1519–1526.


Vecht C.J., Kerkhof M., Duran-Pena A.: Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist, 2014, 19: 751–759.


Vecht Ch.J., and van Breemen M.: Optimizing therapy of seizures in patients with brain tumors. Neurology, 2006, 67 (Suppl. 4): S10–S13.


Vecht C.J., Wagner G.L., Wilms E.B.: Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol., 2003, 2: 404–409.


Vecht Ch.J. and Wilms E.B.: Seizures in low- and high-grade gliomas: current management and future outlook. Expert Rev. Anticancer Ther., 2010, 10: 663–669.


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


Wallace E.M., O’Reilly M., Twomey M.: A review of the use of antiepileptic drugs in high-grade central nervous system tumors. Am. J. Hosp. Palliat. Care, 2012, 29: 618–621.


Weller M., Gorlia T., Cairncross J.G., van den Bent M.J., Mason W., Belanger K. et al.: Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology, 2011, 77: 1156–1164.


Weller M., Stupp R., Wick W.: Epilepsy meets cancer: when, why, and what to do about it? Lancet Oncol., 2012, 13: e375–e382.


Wells E.M., Gaillard W.D., Packer R.J.: Pediatric brain tumors and epilepsy. Semin. Pediatr. Neurol., 2012, 19: 3–8.


Wen P.Y., Schiff D., Kesari S., Drappatz J., Gigas D.C., Doherty L. et al.: Medical management of patients with brain tumors. J. Neurooncol., 2006, 80: 313–332.


Williams B.J., Suki D., Fox B.D., Pelloski C.E., Maldaun M.V., Sawaya R.E. et al.: Stereotactic radiosurgery for metastatic brain tumors: a comprehensive review of complications. J. Neurosurg., 2009, 111: 439–448.


Wu A.S., Trinh V.T., Suki D., Graham S., Forman A., Weinberg J.S. et al.: A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors. J. Neurosurg., 2013, 118: 873–883.


Wychowski T., Wang H., Buniak L., Henry J.C., Mohile N. et al.: Considerations in prophylaxis for tumor-associated epilepsy: prevention of status epilepticus and tolerability of newer generation AEDs. Clin. Neurol. Neurosurg., 2013, 115: 2365–2369.