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Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients

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Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Introduction

Tumor-related epilepsy may respond to chemotherapy. In a previously-published multi-centre randomized clinical trial of 562 elderly glioblastoma patients, temozolomide plus short-course radiotherapy conferred a survival benefit over radiotherapy alone. Seizure outcomes were not reported.

Methods

We performed an unplanned secondary analysis of this trial’s data. The trial design has been previously reported. Seizures were recorded by clinicians as adverse events and by patients in quality of life questionnaires. A Chi-square test of seizure rates between the two groups (α = 0.05) and a Kaplan–Meier estimator of time-to-first self-reported seizure were planned.

Results

Almost all patients were followed until they died. In the radiotherapy alone group, 68 patients (24%) had a documented or self-reported seizure versus 83 patients (30%) in the temozolomide plus radiotherapy group, Chi-square analysis showed no difference (p = 0.15). Patients receiving radiotherapy alone tended to develop seizures earlier than those receiving temozolomide plus radiotherapy (p = 0.054). Patients with seizures had shorter overall survival than those without seizures (hazard ratio 1.24, p = 0.02).

Conclusions

This study was not powered to detect differences in seizure outcomes, but temozolomide seemed to have minimal impact on seizure control in elderly patients with glioblastoma.

Clinical Trial Registration: NCT00482677 2007-06-05.

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Data availability

The datasets used and analyzed for the current study are available from the corresponding author on reasonable request.

References

  1. Koekkoek JAF, Dirven L, Heimans JJ et al (2015) Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide. J Neurol Neurosurg Psychiatry 86:366–373. https://doi.org/10.1136/jnnp-2014-308136

    Article  PubMed  Google Scholar 

  2. Haggiagi A, Avila EK (2019) Seizure response to temozolomide chemotherapy in patients with WHO grade II oligodendroglioma: a single-institution descriptive study. Neuro-Oncol Pract 6:203–208. https://doi.org/10.1093/nop/npy029

    Article  Google Scholar 

  3. Sherman JH, Moldovan K, Yeoh HK et al (2011) Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 114:1617–1621. https://doi.org/10.3171/2010.12.JNS101602

    Article  PubMed  Google Scholar 

  4. Brada M, Viviers L, Abson C et al (2003) Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 14:1715–1721. https://doi.org/10.1093/annonc/mdg371

    Article  PubMed  CAS  Google Scholar 

  5. Pace A, Vidiri A, Galiè E et al (2003) Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann Oncol 14:1722–1726. https://doi.org/10.1093/annonc/mdg502

    Article  PubMed  CAS  Google Scholar 

  6. Avila EK, Chamberlain M, Schiff D et al (2017) Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro-Oncol 19:12–21. https://doi.org/10.1093/neuonc/now190

    Article  PubMed  Google Scholar 

  7. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330

    Article  CAS  Google Scholar 

  8. Perry JR, Laperriere N, O’Callaghan CJ et al (2017) Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 376:1027–1037. https://doi.org/10.1056/NEJMoa1611977

    Article  PubMed  CAS  Google Scholar 

  9. Vecht CJ, Kerkhof M, Duran-Pena A (2014) Seizure prognosis in brain tumors: New insights and evidence-based management. Oncologist 19:751–759. https://doi.org/10.1634/theoncologist.2014-0060

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Forsgren L, Bucht G, Eriksson S, Bergmark L (1996) Incidence and clinical characterization of unprovoked seizures in adults: A prospective population-based study. Epilepsia 37:224–229. https://doi.org/10.1111/j.1528-1157.1996.tb00017.x

    Article  PubMed  CAS  Google Scholar 

  11. Perucca P, Camfield P, Camfield C (2014) Does gender influence susceptibility and consequences of acquired epilepsies? Neurobiol Dis 72:125–130. https://doi.org/10.1016/j.nbd.2014.05.016

    Article  PubMed  Google Scholar 

  12. Bruna J, Miró J, Velasco R (2013) Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment. Expert Rev Clin Pharmacol 6:333–344. https://doi.org/10.1586/ecp.13.12

    Article  PubMed  CAS  Google Scholar 

  13. Greene C, Hanley N, Campbell M (2019) Claudin-5: gatekeeper of neurological function. Fluids Barriers CNS 16:1–15. https://doi.org/10.1186/s12987-019-0123-z

    Article  Google Scholar 

  14. Friedman A (2011) Blood–brain barrier dysfunction, status epilepticus, seizures, and epilepsy: A puzzle of a chicken and egg? Epilepsia 52:19–20. https://doi.org/10.1111/j.1528-1167.2011.03227.x

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chen H, Judkins J, Thomas C et al (2017) Mutant IDH1 and seizures in patients with glioma. Neurology 88:1805–1813. https://doi.org/10.1212/WNL.0000000000003911

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Werhahn KJ (2009) Epilepsy in the elderly. Dtsch Arzteblatt Int 106:135–142. https://doi.org/10.3238/arztebl.2009.0135

    Article  Google Scholar 

  17. Werhahn KJ, Trinka E, Dobesberger J et al (2015) A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy. Epilepsia 56:450–459. https://doi.org/10.1111/epi.12926

    Article  PubMed  CAS  Google Scholar 

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Funding

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Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G2M9, Canada

    Seth A. Climans, Normand Laperriere & Warren P. Mason

  2. Azienda Unità Sanitaria Locale – Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche, Bologna, Italy

    Alba A. Brandes

  3. University of Calgary, Calgary, Canada

    J. Gregory Cairncross

  4. The Canadian Cancer Trials Group, Queen’s University, Kingston, Canada

    Keyue Ding, Christopher J. O’Callaghan & Chad Winch

  5. University of Newcastle, Newcastle, Australia

    Michael Fay

  6. University of Queensland, Brisbane, Australia

    Michael Fay

  7. Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Canada

    Normand Laperriere

  8. University Hospital Gasthuisberg, Leuven, Belgium

    Johan Menten

  9. Saitama Medical University International Medical Center, Saitama, Japan

    Ryo Nishikawa

  10. Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada

    James R. Perry

  11. Peter MacCallum Cancer Centre, Melbourne, Australia

    Claire Phillips

  12. University of Alberta, Edmonton, Canada

    Wilson Roa

  13. Neurology Clinic, University of Heidelberg and Neurooncology Program, German Cancer Research Center, Heidelberg, Germany

    Wolfgang Wick

Authors
  1. Seth A. Climans
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  2. Alba A. Brandes
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  3. J. Gregory Cairncross
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  4. Keyue Ding
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  5. Michael Fay
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  6. Normand Laperriere
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  7. Johan Menten
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  8. Ryo Nishikawa
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  9. Christopher J. O’Callaghan
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  10. James R. Perry
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  11. Claire Phillips
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  12. Wilson Roa
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  13. Wolfgang Wick
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  14. Chad Winch
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  15. Warren P. Mason
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Contributions

All authors interpreted the data and revised the manuscript for intellectual content. S.C., C.O., and W.M. contributed to the study conception and design. Data collection and analysis were performed by A.A.B., G.C., M.F., N.L., J.M., R.N., J.P., C.P., W.R., W.W., and W.M. The statistical analysis was performed by K.D. The first draft of the manuscript was written by S.C. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Seth A. Climans.

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Conflict of interest

The authors declare that we have no conflict of interest.

Ethical approval

This trial was approved by each institutional review board of participating institutions. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent to participate

Each patient provided written informed consent.

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Climans, S.A., Brandes, A.A., Cairncross, J.G. et al. Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients. J Neurooncol 149, 65–71 (2020). https://doi.org/10.1007/s11060-020-03573-x

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  • DOI: https://doi.org/10.1007/s11060-020-03573-x

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