Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients
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CLINICAL STUDY
Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients Seth A. Climans1 · Alba A. Brandes2 · J. Gregory Cairncross3 · Keyue Ding4 · Michael Fay5,6 · Normand Laperriere1,7 · Johan Menten8 · Ryo Nishikawa9 · Christopher J. O’Callaghan4 · James R. Perry10 · Claire Phillips11 · Wilson Roa12 · Wolfgang Wick13 · Chad Winch4 · Warren P. Mason1 Received: 3 May 2020 / Accepted: 24 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 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. Keywords Glioblastoma · Temozolomide · Randomized controlled trial · Seizures · Epilepsy
* Seth A. Climans [email protected] 1
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G2M9, Canada
Azienda Unità Sanitaria Locale – Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche, Bologna, Italy
2
7
Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Canada
8
University Hospital Gasthuisberg, Leuven, Belgium
9
Saitama Medical University International Medical Center, Saitama, Japan
10
Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
11
Peter MacCallum Cancer Centre, Melbourne, Australia
3
University of Calgary, Calgary, Canada
12
4
The Canadian Cancer Trials Group, Queen’s University, Kingston, Canada
University of Alberta, Edmonton, Canada
13
5
University of Newcastle, Newcastle, Australia
Neurology Clinic, University of Heidelberg and Neurooncology Program, German Cancer Research Center, Heide
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