Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study.
Aged
Angiotensin II Type 1 Receptor Blockers
/ therapeutic use
Anti-Inflammatory Agents
/ administration & dosage
Brain Neoplasms
/ pathology
Chemoradiotherapy
/ mortality
Double-Blind Method
Drug Therapy, Combination
Edema
/ epidemiology
Female
Follow-Up Studies
France
/ epidemiology
Glioblastoma
/ pathology
Humans
Incidence
Losartan
/ therapeutic use
Male
Middle Aged
Prednisone
/ administration & dosage
Prognosis
Prospective Studies
Survival Rate
Angiotensin receptor blockers
Glioblastoma
Losartan
Peritumoural oedema
Steroids
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
26
10
2018
revised:
18
12
2018
accepted:
23
12
2018
pubmed:
5
2
2019
medline:
22
5
2020
entrez:
5
2
2019
Statut:
ppublish
Résumé
Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour-related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.
Sections du résumé
BACKGROUND
Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour-related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM.
PATIENTS AND METHODS
Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival.
RESULTS
Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms.
CONCLUSIONS
Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.
Identifiants
pubmed: 30716716
pii: S0959-8049(19)30003-6
doi: 10.1016/j.ejca.2018.12.025
pii:
doi:
Substances chimiques
Angiotensin II Type 1 Receptor Blockers
0
Anti-Inflammatory Agents
0
Losartan
JMS50MPO89
Prednisone
VB0R961HZT
Banques de données
ClinicalTrials.gov
['NCT01805453']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129-136Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.