Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma.
- Seystahl K Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland. katharina.seystahl@usz.ch.
- Hentschel B Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
- Loew S Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
- Gramatzki D Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
- Felsberg J Department of Neuropathology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
- Herrlinger U Department of Neurology, Division of Clinical Neuro-oncology, University of Bonn Medical Center, Bonn, Germany.
- Westphal M Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Schackert G Department of Neurosurgery, Carl Gustav Carus University Hospital, Technical University of Dresden, Dresden, Germany.
- Thon N Department of Neurosurgery, University of Munich LMU, Munich, Germany.
- Tatagiba M Department of Neurosurgery, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
- Pietsch T Department of Neuropathology, Brain Tumor Reference Center of the German Society of Neuropathology and Neuroanatomy, University of Bonn, Bonn, Germany.
- Reifenberger G Department of Neuropathology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
- Löffler M Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
- Wick W Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
- Weller M Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
- 2019-11-23
Published in:
- Journal of cancer research and clinical oncology. - 2020
Bevacizumab
Chemotherapy
Glioblastoma
Nitrosourea
Temozolomide
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Immunological
Bevacizumab
Brain Neoplasms
DNA Methylation
DNA Modification Methylases
DNA Repair Enzymes
Female
Glioblastoma
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Progression-Free Survival
Promoter Regions, Genetic
Retrospective Studies
Tumor Suppressor Proteins
Young Adult
English
BACKGROUND
The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.
METHODS
We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O6-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression.
RESULTS
Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002).
CONCLUSIONS
This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.
The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.
METHODS
We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O6-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression.
RESULTS
Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002).
CONCLUSIONS
This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1007/s00432-019-03086-9
- PMID 31754832
- Persistent URL
- https://sonar.ch/global/documents/47615
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