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

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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.

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References

  1. 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.

    Article  Google Scholar 

  2. van Breemen MSM, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol. 2007;6(5):421–30.

    Article  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. Villemure JG, de Tribolet N. Epilepsy in patients with central nervous system tumors. Curr Opin Neurol. 1996;9(6):424–8.

    Article  CAS  Google Scholar 

  7. Riva M. Epilepsy in neuro-oncology: a review. Eur J Oncol. 2016;21(3):143–56.

    Google Scholar 

  8. Plotkin SR, Wen PY. Neurologic complications of cancer therapy. Neurol Clin NA. 2003;21(1):279–318.

    Article  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. Neef C, de Voogd-van der Straaten I. An interaction between cytostatic and anticonvulsant drugs. Clin Pharmacol Ther. 1988;43(4):372–5.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. Huberfeld G, Vecht CJ. Seizures and gliomas—towards a single therapeutic approach. Nat Rev Neurol. 2016;12(4):204–16.

    Article  Google Scholar 

  15. Browne TR. Pharmacokinetics of antiepileptic drugs. Neurology. 1998;51(5 Suppl 4):S2–7.

    Article  CAS  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. 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.

    Article  CAS  Google Scholar 

  18. 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.

    Article  CAS  Google Scholar 

  19. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer. 2006;6(7):546–58.

    Article  CAS  Google Scholar 

  20. 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.

    Article  Google Scholar 

  21. Yap KY-L, Chui WK, Chan A. Drug interactions between chemotherapeutic regimens and antiepileptics. Clin Ther. 2008;30(8):1385–407.

    Article  CAS  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. Cacho-Diaz B, Lorenzana-Mendoza NA. Valproic acid in patients with glioma: a small review. Clin Oncol. 2017;2:1186–8.

    Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. Vecht CJ, Kerkhof M, Duran-Pena A. Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist. 2014;19(7):751–9.

    Article  CAS  Google Scholar 

  28. Guthrie GD, Eljamel S. Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme. J Neurosurg. 2013;118(4):859–65.

    Article  CAS  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. Beutler AS, Li S, Nicol R, Walsh MJ. Carbamazepine is an inhibitor of histone deacetylases. Life Sci. 2005;76(26):3107–15.

    Article  CAS  Google Scholar 

  31. 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.

    Google Scholar 

  32. 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.

    Article  CAS  Google Scholar 

  33. 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.

    Article  CAS  Google Scholar 

  34. 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.

    Article  Google Scholar 

  35. 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.

    Article  CAS  Google Scholar 

  36. 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.

    Article  Google Scholar 

  37. 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.

    Article  Google Scholar 

  38. 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.

    Article  CAS  Google Scholar 

  39. Lin X, DeAngelis LM. Treatment of brain metastases. J Clin Oncol. 2015;33(30):3475–84.

    Article  CAS  Google Scholar 

  40. 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.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank “Nature Research Editing Service” (Certificate 93D9-5419-D40F-1EF8-A742) for the English language review.

Funding

This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Neuroscience Unit, Neuro-oncology Service, Instituto Nacional de Cancerología, Avenida San Fernando 22 Col, Sección XVI, Tlalpan, Mexico City, 14080, Mexico

    B. Cacho-Diaz, K. Salmeron, C. Boyzo & N. Lorenzana-Mendoza

  2. Clinical Research Department, National Institute of Neurology and Neurosurgery, Mexico City, Mexico

    D. San-Juan

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  1. B. Cacho-Diaz
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  2. D. San-Juan
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  3. K. Salmeron
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Correspondence to B. Cacho-Diaz.

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The authors declared that they have no conflict of interest.

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Institutional ethics and scientific committee approved this research. All procedures performed in studies involving humans were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Cacho-Diaz, B., San-Juan, D., Salmeron, K. et al. Choice of antiepileptic drugs affects the outcome in cancer patients with seizures. Clin Transl Oncol 20, 1571–1576 (2018). https://doi.org/10.1007/s12094-018-1892-6

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  • DOI: https://doi.org/10.1007/s12094-018-1892-6

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