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Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis.

Authors
  • Seliger, Corinna1
  • Genbrugge, Els2
  • Gorlia, Thierry2
  • Chinot, Olivier3
  • Stupp, Roger4
  • Nabors, Burt5
  • Weller, Michael6
  • Hau, Peter1
  • 1 Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany. , (Germany)
  • 2 EORTC Headquarters, Brussels, Belgium. , (Belgium)
  • 3 Aix-Marseille University, APHM, CNRS, INP, Institute of Neurophysiopathology, CHU Timone, Service de Neuro-Oncologie, Marseille, France. , (France)
  • 4 Malnati Brain Tumor Institute of the Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
  • 5 Department of Neurology and Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
  • 6 Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland. , (Switzerland)
Type
Published Article
Journal
International Journal of Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2020
Volume
146
Issue
3
Pages
803–809
Identifiers
DOI: 10.1002/ijc.32337
PMID: 30980539
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Metformin has been linked to improve survival of patients with various cancers. There is little information on survival of glioblastoma patients after use of metformin. We assessed the association between metformin use and survival in a pooled analysis of patient data from 1,731 individuals from the randomized AVAglio, CENTRIC and CORE trials. We performed multivariate Cox analyses for overall survival (OS) and progression-free survival (PFS) comparing patients' use of metformin at baseline and/or during concomitant radiochemotherapy (TMZ/RT). Further exploratory analyses investigated the effect of metformin with a history of diabetes and nonfasting glucose levels in relation to OS or PFS of glioblastoma patients. Metformin alone or in any combination was not significantly associated with OS or PFS (at baseline, hazard ratio [HR] for OS = 0.87; 95% confidence interval [CI] = 0.65-1.16; HR for PFS = 0.84; 95% CI = 0.64-1.10; during TMZ/RT HR for OS = 0.97; 95% CI = 0.68-1.38; HR for PFS = 1.02; 95% CI = 0.74-1.41). We found a statistically nonsignificant association of metformin monotherapy with glioblastoma survival at baseline (HR for OS = 0.68; 95% CI = 0.42-1.10; HR for PFS = 0.57; 95% CI = 0.36-0.91), but not during the TMZ/RT period (HR for OS = 0.90; 95% CI = 0.51-1.56; HR for PFS = 1.05; 95% CI = 0.64-1.73). Diabetes mellitus or increased nonfasting glucose levels were not associated with a difference in OS or PFS in our selected study population. Metformin did not prolong survival of patients with newly diagnosed glioblastoma in our analysis. Additional studies may identify patients with specific tumor characteristics that are associated with potential benefit from treatment with metformin, possibly due to metabolic vulnerabilities. © 2019 UICC.

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