Skip to main content
Top
Published in: Clinical and Translational Oncology 12/2018

01-12-2018 | Research Article

Choice of antiepileptic drugs affects the outcome in cancer patients with seizures

Authors: B. Cacho-Diaz, D. San-Juan, K. Salmeron, C. Boyzo, N. Lorenzana-Mendoza

Published in: Clinical and Translational Oncology | Issue 12/2018

Login to get access

Abstract

Background

Seizures in cancer patients may occur as a result of CNS primary or metastatic tumor, brain surgery, vascular disease, pharmacologic treatment (including chemotherapy), radiation therapy, or metabolic disorders. The aims of the study were to a) determine whether seizures in cancer patients have prognostic implications and b) study patient outcome based on the antiepileptic drug used.

Method

This is a prospective comparative study that included adult cancer patients with and without seizures from May 2010 to November 2016 seen by the neuro-oncology unit at a cancer referral center. Variables included age, gender, oncologic characteristics, seizure features, treatment, and outcome. Parametric and non-parametric tests were used to compare groups, and Kaplan–Meier curves with the log-rank test were used to analyze survival. Cox multivariate regression tests were used to describe survival and compare groups.

Results

A total of 823 patients were included; 419 (51%) patients had at least one seizure and were compared with 404 (49%) who did not experience seizures. Of the seizure group, 53% had brain metastases, 36% did not have a brain tumor, and 11% had a primary brain tumor. No survival differences were noted among patients with brain metastases or primary tumor with or without seizures. In the seizure group, 249 (59%) required only one antiepileptic drug, whereas 134 (32%) required 2 or more. A better overall survival was identified for patients prescribed carbamazepine (p = 0.02), lamotrigine (p = 0.015), levetiracetam (p = 0.03), and valproic acid (p = 0.009).

Conclusions

Patients with primary or metastatic brain tumors have the same overall survival with or without seizures. However, patients with seizures not treated with antiepileptics exhibit worse overall survival.
Literature
1.
go back to reference Bénit CP, Vecht CJ. Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids. Neuro Oncol Pract. 2016;3(4):245–60.CrossRef Bénit CP, Vecht CJ. Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids. Neuro Oncol Pract. 2016;3(4):245–60.CrossRef
2.
go back to reference van Breemen MSM, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol. 2007;6(5):421–30.CrossRef van Breemen MSM, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol. 2007;6(5):421–30.CrossRef
3.
go back to reference Pallud J, Audureau E, Blonski M, Sanai N, Bauchet L, Fontaine D, et al. Epileptic seizures in diffuse low-grade gliomas in adults. Brain. 2014;137(2):449–62.CrossRef Pallud J, Audureau E, Blonski M, Sanai N, Bauchet L, Fontaine D, et al. Epileptic seizures in diffuse low-grade gliomas in adults. Brain. 2014;137(2):449–62.CrossRef
4.
go back to reference Soffietti R, Cornu P, Delattre JY, Grant R, Graus F, Grisold W, et al. EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur J Neurol. 2006;13(7):674–81.CrossRef Soffietti R, Cornu P, Delattre JY, Grant R, Graus F, Grisold W, et al. EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur J Neurol. 2006;13(7):674–81.CrossRef
5.
go back to reference Koekkoek JAF, Kerkhof M, Dirven L, Heimans JJ, Reijneveld JC, Taphoorn MJB. Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review. Neuro Oncol. 2015;17(7):924–34.CrossRef Koekkoek JAF, Kerkhof M, Dirven L, Heimans JJ, Reijneveld JC, Taphoorn MJB. Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review. Neuro Oncol. 2015;17(7):924–34.CrossRef
6.
go back to reference Villemure JG, de Tribolet N. Epilepsy in patients with central nervous system tumors. Curr Opin Neurol. 1996;9(6):424–8.CrossRef Villemure JG, de Tribolet N. Epilepsy in patients with central nervous system tumors. Curr Opin Neurol. 1996;9(6):424–8.CrossRef
7.
go back to reference Riva M. Epilepsy in neuro-oncology: a review. Eur J Oncol. 2016;21(3):143–56. Riva M. Epilepsy in neuro-oncology: a review. Eur J Oncol. 2016;21(3):143–56.
8.
go back to reference Plotkin SR, Wen PY. Neurologic complications of cancer therapy. Neurol Clin NA. 2003;21(1):279–318.CrossRef Plotkin SR, Wen PY. Neurologic complications of cancer therapy. Neurol Clin NA. 2003;21(1):279–318.CrossRef
9.
go back to reference Chang EF, Potts MB, Keles GE, Lamborn KR. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg. 2008;108(2):227–35.CrossRef Chang EF, Potts MB, Keles GE, Lamborn KR. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg. 2008;108(2):227–35.CrossRef
10.
go back to reference Lote K, Stenwig AE, Skullerud K, Hirschberg H. Original paper prevalence and prognostic significance of epilepsy in patients with gliomas. Eur J Cancer. 1998;34(1):98–102.CrossRef Lote K, Stenwig AE, Skullerud K, Hirschberg H. Original paper prevalence and prognostic significance of epilepsy in patients with gliomas. Eur J Cancer. 1998;34(1):98–102.CrossRef
11.
go back to reference Chalk JB, Ridgeway K, Brophy T, Yelland JD, Eadie MJ. Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients. J Neurol Neurosurg Psychiatry. 1984;47(10):1087–90.CrossRef Chalk JB, Ridgeway K, Brophy T, Yelland JD, Eadie MJ. Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients. J Neurol Neurosurg Psychiatry. 1984;47(10):1087–90.CrossRef
12.
go back to reference Neef C, de Voogd-van der Straaten I. An interaction between cytostatic and anticonvulsant drugs. Clin Pharmacol Ther. 1988;43(4):372–5.CrossRef Neef C, de Voogd-van der Straaten I. An interaction between cytostatic and anticonvulsant drugs. Clin Pharmacol Ther. 1988;43(4):372–5.CrossRef
13.
go back to reference Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, 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. 2000;54:1886–93.CrossRef Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, 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. 2000;54:1886–93.CrossRef
14.
go back to reference Huberfeld G, Vecht CJ. Seizures and gliomas—towards a single therapeutic approach. Nat Rev Neurol. 2016;12(4):204–16.CrossRef Huberfeld G, Vecht CJ. Seizures and gliomas—towards a single therapeutic approach. Nat Rev Neurol. 2016;12(4):204–16.CrossRef
15.
go back to reference Browne TR. Pharmacokinetics of antiepileptic drugs. Neurology. 1998;51(5 Suppl 4):S2–7.CrossRef Browne TR. Pharmacokinetics of antiepileptic drugs. Neurology. 1998;51(5 Suppl 4):S2–7.CrossRef
16.
go back to reference Wegman-Ostrosky T, Reynoso-Noverón N, Mejía-Pérez SI, Sánchez-Correa TE, Alvarez-Gómez RM, Vidal-Millán S, et al. Clinical prognostic factors in adults with astrocytoma: Historic cohort. Clin Neurol Neurosurg. 2016;146:116–22.CrossRef Wegman-Ostrosky T, Reynoso-Noverón N, Mejía-Pérez SI, Sánchez-Correa TE, Alvarez-Gómez RM, Vidal-Millán S, et al. Clinical prognostic factors in adults with astrocytoma: Historic cohort. Clin Neurol Neurosurg. 2016;146:116–22.CrossRef
17.
go back to reference Riva M, Salmaggi A, Marchioni E, Silvani A, Tomei G, Lorusso L, et al. Tumour-associated epilepsy: clinical impact and the role of referring centres in a cohort of glioblastoma patients. A multicentre study from the Lombardia Neurooncology Group. Neurol Sci. 2006;27(5):345–51.CrossRef Riva M, Salmaggi A, Marchioni E, Silvani A, Tomei G, Lorusso L, et al. Tumour-associated epilepsy: clinical impact and the role of referring centres in a cohort of glioblastoma patients. A multicentre study from the Lombardia Neurooncology Group. Neurol Sci. 2006;27(5):345–51.CrossRef
18.
go back to reference Chen H, Judkins J, Thomas C, Wu M, Khoury L, Benjamin CG, et al. Mutant IDH1 and seizures in patients with glioma. Neurology. 2017;88(19):1805–13.CrossRef Chen H, Judkins J, Thomas C, Wu M, Khoury L, Benjamin CG, et al. Mutant IDH1 and seizures in patients with glioma. Neurology. 2017;88(19):1805–13.CrossRef
19.
go back to reference Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer. 2006;6(7):546–58.CrossRef Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer. 2006;6(7):546–58.CrossRef
20.
go back to reference Singh G, Rees JH, Sander JW. Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment. J Neurol Neurosurg Psychiatry. 2006;78(4):342–9.CrossRef Singh G, Rees JH, Sander JW. Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment. J Neurol Neurosurg Psychiatry. 2006;78(4):342–9.CrossRef
21.
go back to reference Yap KY-L, Chui WK, Chan A. Drug interactions between chemotherapeutic regimens and antiepileptics. Clin Ther. 2008;30(8):1385–407.CrossRef Yap KY-L, Chui WK, Chan A. Drug interactions between chemotherapeutic regimens and antiepileptics. Clin Ther. 2008;30(8):1385–407.CrossRef
22.
go back to reference 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(3):255–60.CrossRef 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(3):255–60.CrossRef
23.
go back to reference Kerkhof M, Dielemans JCM, van Breemen MS, Zwinkels H, Walchenbach R, Taphoorn MJ, et al. Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro Oncol. 2013;15(7):961–7.CrossRef Kerkhof M, Dielemans JCM, van Breemen MS, Zwinkels H, Walchenbach R, Taphoorn MJ, et al. Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro Oncol. 2013;15(7):961–7.CrossRef
24.
go back to reference Happold C, Gorlia T, Chinot O, Gilbert MR, Nabors LB, Wick W, et al. Does valproic acid or levetiracetam improve survival in glioblastoma? A pooled analysis of prospective clinical trials in newly diagnosed glioblastoma. J Clin Oncol. 2016;34(7):731–9.CrossRef Happold C, Gorlia T, Chinot O, Gilbert MR, Nabors LB, Wick W, et al. Does valproic acid or levetiracetam improve survival in glioblastoma? A pooled analysis of prospective clinical trials in newly diagnosed glioblastoma. J Clin Oncol. 2016;34(7):731–9.CrossRef
25.
go back to reference Cacho-Diaz B, Lorenzana-Mendoza NA. Valproic acid in patients with glioma: a small review. Clin Oncol. 2017;2:1186–8. Cacho-Diaz B, Lorenzana-Mendoza NA. Valproic acid in patients with glioma: a small review. Clin Oncol. 2017;2:1186–8.
26.
go back to reference Gefroh-Grimes HA, Gidal BE. Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics. Acta Neurol Scand. 2015;133(1):4–16.CrossRef Gefroh-Grimes HA, Gidal BE. Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics. Acta Neurol Scand. 2015;133(1):4–16.CrossRef
27.
go back to reference Vecht CJ, Kerkhof M, Duran-Pena A. Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist. 2014;19(7):751–9.CrossRef Vecht CJ, Kerkhof M, Duran-Pena A. Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist. 2014;19(7):751–9.CrossRef
28.
go back to reference Guthrie GD, Eljamel S. Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme. J Neurosurg. 2013;118(4):859–65.CrossRef Guthrie GD, Eljamel S. Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme. J Neurosurg. 2013;118(4):859–65.CrossRef
29.
go back to reference Jaeckle KA, Ballman K, Furth A, Buckner JC. Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma. Neurology. 2009;73(15):1207–13.CrossRef Jaeckle KA, Ballman K, Furth A, Buckner JC. Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma. Neurology. 2009;73(15):1207–13.CrossRef
30.
go back to reference Beutler AS, Li S, Nicol R, Walsh MJ. Carbamazepine is an inhibitor of histone deacetylases. Life Sci. 2005;76(26):3107–15.CrossRef Beutler AS, Li S, Nicol R, Walsh MJ. Carbamazepine is an inhibitor of histone deacetylases. Life Sci. 2005;76(26):3107–15.CrossRef
31.
go back to reference Nevitt SJ, Tudur Smith C, Weston J, Marson AG. Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev. 2016;11:CD001031. Nevitt SJ, Tudur Smith C, Weston J, Marson AG. Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev. 2016;11:CD001031.
32.
go back to reference Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000–15.CrossRef Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000–15.CrossRef
33.
go back to reference Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016–26.CrossRef Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016–26.CrossRef
34.
go back to reference Taing KD, O’Brien TJ, Williams DA, French CR. Anti-epileptic drug combination efficacy in an in vitro seizure model—phenytoin and valproate, lamotrigine and valproate. PLoS One. 2017;12(1):e0169974.CrossRef Taing KD, O’Brien TJ, Williams DA, French CR. Anti-epileptic drug combination efficacy in an in vitro seizure model—phenytoin and valproate, lamotrigine and valproate. PLoS One. 2017;12(1):e0169974.CrossRef
35.
go back to reference Mauro AM, Bomprezzi C, Morresi S, Provinciali L, Formica F, Iacoangeli M, et al. Prevention of early postoperative seizures in patients with primary brain tumors: preliminary experience with oxcarbazepine. J Neurooncol. 2007;81(3):279–85.CrossRef Mauro AM, Bomprezzi C, Morresi S, Provinciali L, Formica F, Iacoangeli M, et al. Prevention of early postoperative seizures in patients with primary brain tumors: preliminary experience with oxcarbazepine. J Neurooncol. 2007;81(3):279–85.CrossRef
36.
go back to reference Maschio M, Dinapoli L, Vidiri A, Pace A, Fabi A, Pompili 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. 2009;28(1):60.CrossRef Maschio M, Dinapoli L, Vidiri A, Pace A, Fabi A, Pompili 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. 2009;28(1):60.CrossRef
37.
go back to reference Dogan EA, Usta BE, Bilgen R, Senol Y, Aktekin B. Efficacy, tolerability, and side effects of oxcarbazepine monotherapy: a prospective study in adult and elderly patients with newly diagnosed partial epilepsy. Epilepsy Behav. 2008;13(1):156–61.CrossRef Dogan EA, Usta BE, Bilgen R, Senol Y, Aktekin B. Efficacy, tolerability, and side effects of oxcarbazepine monotherapy: a prospective study in adult and elderly patients with newly diagnosed partial epilepsy. Epilepsy Behav. 2008;13(1):156–61.CrossRef
38.
go back to reference 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 Neurooncol. 2012;106(3):651–6.CrossRef 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 Neurooncol. 2012;106(3):651–6.CrossRef
39.
go back to reference Lin X, DeAngelis LM. Treatment of brain metastases. J Clin Oncol. 2015;33(30):3475–84.CrossRef Lin X, DeAngelis LM. Treatment of brain metastases. J Clin Oncol. 2015;33(30):3475–84.CrossRef
40.
go back to reference Avila EK, Chamberlain M, Schiff D, Reijneveld JC, Armstrong TS, Ruda R, et al. Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro Oncol. 2016;19(1):12–21.CrossRef Avila EK, Chamberlain M, Schiff D, Reijneveld JC, Armstrong TS, Ruda R, et al. Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro Oncol. 2016;19(1):12–21.CrossRef
Metadata
Title
Choice of antiepileptic drugs affects the outcome in cancer patients with seizures
Authors
B. Cacho-Diaz
D. San-Juan
K. Salmeron
C. Boyzo
N. Lorenzana-Mendoza
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 12/2018
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-018-1892-6

Other articles of this Issue 12/2018

Clinical and Translational Oncology 12/2018 Go to the issue

Correspondence

Letter to the Editor

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine