Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis.
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Brain Neoplasms
/ mortality
Chemoradiotherapy
Female
Glioblastoma
/ mortality
Humans
Kaplan-Meier Estimate
Male
Metformin
/ therapeutic use
Middle Aged
Progression-Free Survival
Randomized Controlled Trials as Topic
Temozolomide
/ therapeutic use
Young Adult
drug repurposing
glioblastoma
metformin
overall survival
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
received:
11
01
2019
revised:
11
03
2019
accepted:
18
03
2019
pubmed:
14
4
2019
medline:
12
2
2020
entrez:
14
4
2019
Statut:
ppublish
Résumé
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.
Substances chimiques
Antineoplastic Agents, Alkylating
0
Metformin
9100L32L2N
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
803-809Informations de copyright
© 2019 UICC.
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