Top

Published in:

01-08-2020 | Glioblastoma | Clinical Study

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

Authors: Seth A. Climans, Alba A. Brandes, J. Gregory Cairncross, Keyue Ding, Michael Fay, Normand Laperriere, Johan Menten, Ryo Nishikawa, Christopher J. O’Callaghan, James R. Perry, Claire Phillips, Wilson Roa, Wolfgang Wick, Chad Winch, Warren P. Mason

Published in: Journal of Neuro-Oncology | Issue 1/2020

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.

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-2014-308136CrossRefPubMed

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/npy029CrossRef

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.JNS101602CrossRefPubMed

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/mdg371CrossRefPubMed

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/mdg502CrossRefPubMed

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/now190CrossRefPubMed

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/NEJMoa043330CrossRef

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/NEJMoa1611977CrossRefPubMed

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.2014-0060CrossRefPubMedPubMedCentral

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.xCrossRefPubMed

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.2014.05.016CrossRefPubMed

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.13.12CrossRefPubMed

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-zCrossRef

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.xCrossRefPubMedPubMedCentral

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.0000000000003911CrossRefPubMedPubMedCentral

16.

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

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.12926CrossRefPubMed

Title: Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients
Authors: Seth A. Climans
Alba A. Brandes
J. Gregory Cairncross
Keyue Ding
Michael Fay
Normand Laperriere
Johan Menten
Ryo Nishikawa
Christopher J. O’Callaghan
James R. Perry
Claire Phillips
Wilson Roa
Wolfgang Wick
Chad Winch
Warren P. Mason
Publication date: 01-08-2020
Publisher: Springer US
Keywords: Glioblastoma
Glioma
Glioma
Glioblastoma
Radiotherapy
Epilepsy
Glioblastoma
Glioma
Published in: Journal of Neuro-Oncology / Issue 1/2020
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-020-03573-x

At a glance: The STEP trials

Springer Medicine

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

Abstract

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Autoimmune disease-related primary CNS lymphoma: systematic review and meta-analysis

Racial and socioeconomic disparities differentially affect overall and cause-specific survival in glioblastoma

Impact of insurance on hospital course and readmission after resection of benign meningioma

Pontine gliomas a 10-year population-based study: a report from The Canadian Paediatric Brain Tumour Consortium (CPBTC)

Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas

Minimally invasive resection of intracranial lesions using tubular retractors: a large, multi-surgeon, multi-institutional series