Epilepsy in glioblastoma patients: Basic mechanisms and current problems in treatment

Expert Review of Clinical Pharmacology

Volumn 6, Issue 3, 2013, Pages 333-344

  Bruna, Jordi ^a,b   Miró, Júlia ^a   Velasco, Roser ^a,b  

^a HOSPITAL UNIVERSITARI DE BELLVITGE   (Spain)

^b INSTITUT DE NEUROCIÈNCIES   (Spain)

Author keywords

high grade glioma; prophylaxis; seizures

Indexed keywords

ANTICONVULSIVE AGENT; ANTINEOPLASTIC AGENT; CARBAMAZEPINE; CARMUSTINE; CISPLATIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; ENZASTAURIN; ERLOTINIB; ETOPOSIDE; FIRTECAN; GEFITINIB; IMATINIB; IRINOTECAN; MARIMASTAT; NITROSOUREA DERIVATIVE; PHENYTOIN; SORAFENIB; TAXANE DERIVATIVE; TEMOZOLOMIDE; TEMSIROLIMUS; THIOTEPA; TIPIFARNIB; TOPIRAMATE; TOPOTECAN; UNINDEXED DRUG; VALPROIC ACID; VATALANIB; VINCRISTINE; ZONISAMIDE;

BLOOD TOXICITY; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; BRAIN DISEASE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURGERY; COGNITIVE DEFECT; DISTRIBUTION VOLUME; DRUG ANTAGONISM; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG GLUCURONIDATION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG RESISTANCE; DRUG UPTAKE; EPILEPSY; EPILEPTOGENESIS; GLIOBLASTOMA; HUMAN; HYPERAMMONEMIC ENCEPHALOPATHY; HYPONATREMIA; MENTAL DISEASE; METABOLIC ACIDOSIS; NEUROCOGNITIVE DECLINE; NEUROTOXICITY; NEUTROPENIA; PARESTHESIA; PROPHYLAXIS; RASH; REVIEW; SEDATION; SEIZURE; SIDE EFFECT; SKIN MANIFESTATION; SOMNOLENCE; STEVENS JOHNSON SYNDROME; SURVIVAL; THROMBOCYTOPENIA;

ANTICONVULSANTS; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; DRUG INTERACTIONS; EPILEPSY; GLIOBLASTOMA; HUMANS; TREATMENT OUTCOME;

EID: 84877621451     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/ecp.13.12     Document Type: Review

References (112)

1. Glantz MJ, Cole BF, Forsyth PA et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 54(10), 1886-1893 (2000).
2. Moots PL, Maciunas RJ, Eisert DR, Parker RA, Laporte K, Abou-Khalil B. The course of seizure disorders in patients with malignant gliomas. Arch. Neurol. 52(7), 717-724 (1995).
3. Lee JW, Wen PY, Hurwitz S et al. Morphological characteristics of brain tumors causing seizures. Arch. Neurol. 67(3), 336-342 (2010).
4. van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol. 6(5), 421-430 (2007).
5. 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. 72(3), 255-260 (2005).
6. Rosati A, Buttolo L, Stefini R, Todeschini A, Cenzato M, Padovani A. Efficacy and safety of levetiracetam in patients with glioma: a clinical prospective study. Arch. Neurol. 67(3), 343-346 (2010).
7. Simó M, Velasco R, Graus F et al. Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy. J. Neurooncol. 108(3), 451-458 (2012).
8. Chang SM, Parney IF, Huang W et al.; Glioma Outcomes Project Investigators. Patterns of care for adults with newly diagnosed malignant glioma. JAMA 293(5), 557-564 (2005).
9. Bauchet L, Mathieu-Daudé H, Fabbro-Peray P et al.; Société Française de Neurochirurgie (SFNC); Club de Neuro-Oncologie of the Société Française de Neurochirurgie (CNO-SFNC); Société Française de Neuropathologie (SFNP); Association des Neuro-Oncologues d'Expression Française (ANOCEF). Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004. Neuro-oncology 12(7), 725-735 (2010).
10. van Breemen MS, Rijsman RM, Taphoorn MJ, Walchenbach R, Zwinkels H, Vecht CJ. Efficacy of anti-epileptic drugs in patients with gliomas and seizures. J. Neurol. 256(9), 1519-1526 (2009).
11. Hildebrand J, Lecaille C, Perennes J, Delattre JY. Epileptic seizures during follow-up of patients treated for primary brain tumors. Neurology 65(2), 212-215 (2005).
12. DeLorenzo RJ, Hauser WA, Towne AR et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 46(4), 1029-1035 (1996).
13. Knake S, Rosenow F, Vescovi M et al.; Status Epilepticus Study Group Hessen (SESGH). Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 42(6), 714-718 (2001).
14. Trinka E, Bauer G, Oberaigner W, Ndayisaba JP, Seppi K, Granbichler CA. Cause-specific mortality among patients with epilepsy: Results from a 30-year cohort study. Epilepsia 54(3), 495-501 (2013).
15. Englot DJ, Berger MS, Barbaro NM, Chang EF. Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia 53(1), 51-57 (2012).
16. Klein M, Engelberts NH, van der Ploeg HM et al. Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life. Ann. Neurol. 54(4), 514-520 (2003).
17. de Groot M, Reijneveld JC, Aronica E, Heimans JJ. Epilepsy in patients with a brain tumour: focal epilepsy requires focused treatment. Brain 135(Pt 4), 1002-1016 (2012).
18. Schaller B, Rüegg SJ. Brain tumor and seizures: pathophysiology and its implications for treatment revisited. Epilepsia 44(9), 1223-1232 (2003).
19. de Groot J, Sontheimer H. Glutamate and the biology of gliomas. Glia 59(8), 1181-1189 (2011).
20. Conti L, Palma E, Roseti C et al. Anomalous levels of Cl-transporters cause a decrease of GABAergic inhibition in human peritumoral epileptic cortex. Epilepsia 52(9), 1635-1644 (2011).
21. Isoardo G, Morra I, Chiarle G et al. Different aquaporin-4 expression in glioblastoma multiforme patients with and without seizures. Mol. Med. 18, 1147-1151 (2012).
22. Gerweck LE, Seetharaman K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res. 56(6), 1194-1198 (1996).
23. Schaller B. Influences of brain tumorassociated pH changes and hypoxia on epileptogenesis. Acta Neurol. Scand. 111(2), 75-83 (2005).
24. Vezzani A, Granata T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46(11), 1724-1743 (2005).
25. Franceschetti S, Binelli S, Casazza M et al. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Acta Neurochir. (Wien) 103(1-2), 47-51 (1990).
26. Boarini DJ, Beck DW, VanGilder JC. Postoperative prophylactic anticonvulsant therapy in cerebral gliomas. Neurosurgery 16(3), 290-292 (1985).
27. Forsyth PA, Weaver S, Fulton D et al. Prophylactic anticonvulsants in patients with brain tumour. Can. J. Neurol. Sci. 30(2), 106-112 (2003).
28. Glantz MJ, Cole BF, Friedberg MH et al. A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Neurology 46(4), 985-991 (1996).
29. Reardon DA. Treatment of elderly patients with glioblastoma. Lancet Oncol. 13(7), 656-657 (2012).
30. Vecht CJ, Wagner GL, Wilms EB. Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol. 2(7), 404-409 (2003).
31. Kreisl TN, Kotliarova S, Butman JA et al. A Phase I/II trial of enzastaurin in patients with recurrent high-grade gliomas. Neuro-oncology 12(2), 181-189 (2010).
32. Prados MD, Yung WK, Wen PY et al. Phase-1 trial of gefitinib and temozolomide in patients with malignant glioma: a North American brain tumor consortium study. Cancer Chemother. Pharmacol. 61(6), 1059-1067 (2008).
33. Pursche S, Schleyer E, von Bonin M et al. Influence of enzyme-inducing antiepileptic drugs on trough level of imatinib in glioblastoma patients. Curr. Clin. Pharmacol. 3(3), 198-203 (2008).
34. Galanis E, Buckner JC, Maurer MJ et al.; North Central Cancer Treatment Group. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J. Clin. Oncol. 23(23), 5294-5304 (2005).
35. Reardon DA, Egorin MJ, Desjardins A et al. Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer 115(10), 2188-2198 (2009).
36. Cloughesy TF, Wen PY, Robins HI et al. Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study. J. Clin. Oncol. 24(22), 3651-3656 (2006).
37. Raizer JJ, Abrey LE, Lassman AB et al.; North American Brain Tumor Consortium. A Phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. Neuro-oncology 12(1), 95-103 (2010).
38. Reardon DA, Vredenburgh JJ, Desjardins A et al. Effect of CYP3A-inducing antiepileptics on sorafenib exposure: results of a Phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J. Neurooncol. 101(1), 57-66 (2011).
39. Friedman HS, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma. Clin. Cancer Res. 6(7), 2585-2597 (2000).
40. Sheth RD. Metabolic concerns associated with antiepileptic medications. Neurology 63(10 Suppl. 4), S24-S29 (2004).
41. Jaeckle KA, Ballman K, Furth A, Buckner JC. Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma. Neurology 73(15), 1207-1213 (2009).
42. Groves MD, Puduvalli VK, Conrad CA et al. Phase II trial of temozolomide plus marimastat for recurrent anaplastic gliomas: a relationship among efficacy, joint toxicity and anticonvulsant status. J. Neurooncol. 80(1), 83-90 (2006).
43. Bourg V, Lebrun C, Chichmanian RM, Thomas P, Frenay M. Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity. Ann. Oncol. 12(2), 217-219 (2001).
44. Gupta E, Wang X, Ramirez J, Ratain MJ. Modulation of glucuronidation of SN-38, the active metabolite of irinotecan, by valproic acid and phenobarbital. Cancer Chemother. Pharmacol. 39(5), 440-444 (1997).
45. Weller M, Gorlia T, Cairncross JG et al. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology 77(12), 1156-1164 (2011).
46. Meijerman I, Beijnen JH, Schellens JH. Combined action and regulation of Phase II enzymes and multidrug resistance proteins in multidrug resistance in cancer. Cancer Treat. Rev. 34(6), 505-520 (2008).
47. Aronica E, Gorter JA, Redeker S et al. Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain. Epilepsia 46(6), 849-857 (2005).
48. Liu JY, Thom M, Catarino CB et al. Neuropathology of the blood-brain barrier and pharmaco-resistance in human epilepsy. Brain 135(Pt 10), 3115-3133 (2012).
49. Alexiou GA, Goussia A, Voulgaris S et al. Prognostic significance of MRP5 immunohistochemical expression in glioblastoma. Cancer Chemother. Pharmacol. 69(5), 1387-1391 (2012).
50. Calatozzolo C, Pollo B, Botturi A et al. Multidrug resistance proteins expression in glioma patients with epilepsy. J. Neurooncol. 110(1), 129-135 (2012).
51. Zhang C, Kwan P, Zuo Z, Baum L. The transport of antiepileptic drugs by P-glycoprotein. Adv. Drug Deliv. Rev. 64(10), 930-942 (2012).
52. Tang R, Faussat AM, Majdak P et al. Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1. Leukemia 18(7), 1246-1251 (2004).
53. Yang HW, Liu HY, Liu X et al. Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro. Neurosci. Lett. 434(3), 299-303 (2008).
54. Eyal S, Lamb JG, Smith-Yockman M et al. The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in human tumour cell lines and in rat liver. Br. J. Pharmacol. 149(3), 250-260 (2006).
55. Pace A, Villani V, Di Lorenzo C et al. Epilepsy in the end-of-life phase in patients with high-grade gliomas. J. Neurooncol. 111(1), 83-86 (2013).
56. Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology 62(1), 23-27 (2004).
57. de Groot M, Douw L, Sizoo EM et al. Levetiracetam improves verbal memory in high-grade glioma patients. Neuro-oncology 15(2), 216-223 (2013).
58. White JR, Walczak TS, Marino SE, Beniak TE, Leppik IE, Birnbaum AK. Zonisamide discontinuation due to psychiatric and cognitive adverse events: a case-control study. Neurology 75(6), 513-518 (2010).
59. Carpay JA, Aldenkamp AP, van Donselaar CA. Complaints associated with the use of antiepileptic drugs: results from a community-based study. Seizure 14(3), 198-206 (2005).
60. Zaccara G, Gangemi PF, Cincotta M. Central nervous system adverse effects of new antiepileptic drugs. A meta-analysis of placebo-controlled studies. Seizure 17(5), 405-421 (2008).
61. Perucca P, Carter J, Vahle V, Gilliam FG. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology 72(14), 1223-1229 (2009).
62. Blackburn SC, Oliart AD, García Rodríguez LA, Pérez Gutthann S. Antiepileptics and blood dyscrasias: a cohort study. Pharmacotherapy 18(6), 1277-1283 (1998).
63. Guthrie GD, Eljamel S. Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme. J. Neurosurg. (2012).
64. Blaheta RA, Cinatl J Jr. Anti-tumor mechanisms of valproate: a novel role for an old drug. Med. Res. Rev. 22(5), 492-511 (2002).
65. Ryu CH, Yoon WS, Park KY et al. Valproic acid downregulates the expression of MGMT and sensitizes temozolomideresistant glioma cells. J. Biomed. Biotechnol. 2012, 987495 (2012).
66. Mockenhaupt M, Messenheimer J, Tennis P, Schlingmann J. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology 64(7), 1134-1138 (2005).
67. Micali G, Linthicum K, Han N, West DP. Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies. Pharmacotherapy 19(2), 223-227 (1999).
68. Sirven JI, Wingerchuk DM, Drazkowski JF, Lyons MK, Zimmerman RS. Seizure prophylaxis in patients with brain tumors: a meta-analysis. Mayo Clin. Proc. 79(12), 1489-1494 (2004).
69. Tremont-Lukats IW, Ratilal BO, Armstrong T, Gilbert MR. Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database Syst. Rev. 2, CD004424 (2008).
70. Kuijlen JM, Teernstra OP, Kessels AG, Herpers MJ, Beuls EA. Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis. Seizure 5(4), 291-298 (1996).
71. De Santis A, Villani R, Sinisi M, Stocchetti N, Perucca E. Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study. Epilepsia 43(2), 175-182 (2002).
72. Milligan TA, Hurwitz S, Bromfield EB. Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery. Neurology 71(9), 665-669 (2008).
73. Kern K, Schebesch KM, Schlaier J et al. Levetiracetam compared to phenytoin for the prevention of postoperative seizures after craniotomy for intracranial tumours in patients without epilepsy. J. Clin. Neurosci. 19(1), 99-100 (2012).
74. Zafar SN, Khan AA, Ghauri AA, Shamim MS. Phenytoin versus Leviteracetam for seizure prophylaxis after brain injury -a meta analysis. BMC Neurol. 12, 30 (2012).
75. Kerrigan S, Grant R. Antiepileptic drugs for treating seizures in adults with brain tumours. Cochrane Database Syst. Rev. 8, CD008586 (2011).
76. Lim DA, Tarapore P, Chang E et al. Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized Phase II pilot study. J. Neurooncol. 93(3), 349-354 (2009).
77. 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(1), 205-214 (2011).
78. Luyken C, Blümcke I, Fimmers R et al. The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects. Epilepsia 44(6), 822-830 (2003).
79. Duffau H, Capelle L, Lopes M, Bitar A, Sichez JP, van Effenterre R. Medically intractable epilepsy from insular low-grade gliomas: improvement after an extended lesionectomy. Acta Neurochir. (Wien) 144(6), 563-572; discussion 572 (2002).
80. Gilmore R, Morris H 3rd, Van Ness PC, Gilmore-Pollak W, Estes M. Mirror focus: function of seizure frequency and influence on outcome after surgery. Epilepsia 35(2), 258-263 (1994).
81. Rogers LR, Morris HH, Lupica K. Effect of cranial irradiation on seizure frequency in adults with low-grade astrocytoma and medically intractable epilepsy. Neurology 43(8), 1599-1601 (1993).
82. Chalifoux R, Elisevich K. Effect of ionizing radiation on partial seizures attributable to malignant cerebral tumors. Stereotact. Funct. Neurosurg. 67(3-4), 169-182 (1997).
83. van den Bent MJ, Afra D, de Witte O et al.; EORTC Radiotherapy and Brain Tumor Groups and the UK Medical Research Council. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366(9490), 985-990 (2005).
84. Schröttner O, Eder HG, Unger F, Feichtinger K, Pendl G. Radiosurgery in lesional epilepsy: brain tumors. Stereotact. Funct. Neurosurg. 70(Suppl. 1), 50-56 (1998).
85. Pace A, Vidiri A, Galiè E et al. Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann. Oncol. 14(12), 1722-1726 (2003).
86. Sherman JH, Moldovan K, Yeoh HK et al. Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J. Neurosurg. 114(6), 1617-1621 (2011).
87. Frenay MP, Fontaine D, Vandenbos F, Lebrun C. First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas. Eur. J. Neurol. 12(9), 685-690 (2005).
88. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 103(1), 2-30 (2013).
89. Friedman HS, Prados MD, Wen PY et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol. 27(28), 4733-4740 (2009).
90. Beyenburg S, Stavem K, Schmidt D. Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: systematic review and meta-analysis. Epilepsia 51(1), 7-26 (2010).
91. Beyenburg S, Stavem K, Schmidt D. Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: systematic review and meta-analysis. Epilepsia 53(3), 512-520 (2012).
92. Wilby J, Kainth A, Hawkins N et al. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation. Health Technol. Assess. 9(15), 1-157, iii-iv (2005).
93. Hanada T, Hashizume Y, Tokuhara N et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia 52(7), 1331-1340 (2011).
94. French JA, Krauss GL, Steinhoff BJ et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global Phase III study 305. Epilepsia 54(1), 117-125 (2013).
95. French JA, Krauss GL, Biton V et al. Adjunctive perampanel for refractory partial-onset seizures: randomized Phase III study 304. Neurology 79(6), 589-596 (2012).
96. Krauss GL, Serratosa JM, Villanueva V et al. Randomized Phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 78(18), 1408-1415 (2012).
97. Wannamaker W, Davies R, Namchuk M et al. (S)-1-((S)-2-{[1-(4-amino-3- chlorophenyl)-methanoyl]-amino}-3,3-dimethylbutanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J. Pharmacol. Exp. Ther. 321(2), 509-516 (2007).
98. Perry JR, Sawka C. Add-on gabapentin for refractory seizures in patients with brain tumours. Can. J. Neurol. Sci. 23(2), 128-131 (1996).
99. Striano S, Striano P, Boccella P, Nocerino C, Bilo L. Tiagabine in glial tumors. Epilepsy Res. 49(1), 81-85 (2002).
100. Maschio M, Dinapoli L, Zarabla A et al. Outcome and tolerability of topiramate in brain tumor associated epilepsy. J. Neurooncol. 86(1), 61-70 (2008).
101. Lu Y, Yu W, Wang X. Efficacy of topiramate in adult patients with symptomatic epilepsy: an open-label, long-term, retrospective observation. CNS Drugs 23(4), 351-359 (2009).
102. Novy J, Stupp R, Rossetti AO. Pregabalin in patients with primary brain tumors and seizures: a preliminary observation. Clin. Neurol. Neurosurg. 111(2), 171-173 (2009).
103. Maschio M, Dinapoli L, Sperati F et al. Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy: a pilot study. Epileptic Disord. 14(4), 388-397 (2012).
104. Maschio M, Dinapoli L, Saveriano F et al. Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report. Acta Neurol. Scand. 120(3), 210-212 (2009).
105. Maschio M, Dinapoli L, Vidiri A et al. 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 (2009).
106. Maschio M, Dinapoli L, Mingoia M et al. Lacosamide as add-on in brain tumorrelated epilepsy: preliminary report on efficacy and tolerability. J. Neurol. 258(11), 2100-2104 (2011).
107. Wagner GL, Wilms EB, Van Donselaar CA, Vecht ChJ. Levetiracetam: preliminary experience in patients with primary brain tumours. Seizure 12(8), 585-586 (2003).
108. Newton HB, Goldlust SA, Pearl D. Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. J. Neurooncol. 78(1), 99-102 (2006).
109. Maschio M, Albani F, Baruzzi A et al. Levetiracetam therapy in patients with brain tumour and epilepsy. J. Neurooncol. 80(1), 97-100 (2006).
110. Bähr O, Hermisson M, Rona S et al. Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial. Acta Neurochir. (Wien) 154(2), 229-235; discussion 235 (2012).
111. Temodar® (temozolomide). www.temodar.com
112. ClinicalTrials.gov. www.clinicaltrials.gov