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Eur J Cancer. 2019 Feb 1;109:129-136. doi: 10.1016/j.ejca.2018.12.025. [Epub ahead of print]

Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study.

Author information

1
Department of Neurology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: renata.ursu@aphp.fr.
2
Department of Neuro-Oncology, Hospices Civils de Lyon, Groupe Hospitalier Est, Lyon, France.
3
Department of Neurology Mazarin, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France.
4
Department of Neuro-Oncology, CHU Timone, Marseille, France; Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
5
University of Lille, Inserm, U-1192, F-59000 Lille, France; CHU Lille, General and Stereotaxic Neurosurgery Service, F-59000 Lille, France; Oscar Lambret Center, Neurology, Medical Oncology Department, F-59000 Lille, France.
6
Department of Neurology, Hôpital d'Instruction des Armées Percy, Service de Santé des Armées, Paris, France.
7
Department of Radiation Oncology, Institut du Cancer de Montpellier, Montpellier cedex 5, France.
8
Department of Neurology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France.
9
Department of Neurology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
10
Centre de Lutte Contre le Cancer Eugène Marquis, F-35042 Rennes, France; INSERM U1242, "Chemistry, Oncogenesis, Stress, Signaling", Université de Rennes 1, Rennes, France.
11
Department of Neuro-Oncology, Hospices Civils de Lyon, Groupe Hospitalier Est, Lyon, France; Department of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
12
AP-HP, Unité de Recherche Clinique, Hôpital Fernand Widal, Université Paris-Diderot, Paris, France.
13
Agence Générale des Equipements et Produits de Santé (AGEPS), Paris, France.
14
Department of Neurosurgery, Lariboisière Hospital, APHP, Paris, France; University Paris 7, Paris, France; IMNC, UMR 8165, Orsay, France.
15
Ramsey Générale de Santé, Institut de Radiothérapie des Hauts-Energies, Bobigny, France.

Abstract

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.

KEYWORDS:

Angiotensin receptor blockers; Glioblastoma; Losartan; Peritumoural oedema; Steroids

PMID:
30716716
DOI:
10.1016/j.ejca.2018.12.025

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