- •A reduced steroid requirement in patients taking angiotensin receptor blockers (ARBs) was reported in a retrospective series.
- •This randomised trial was designed to assess if the addition of ARBs (Losartan) to standard of care can reduce steroid requirement in patients with de novo GBM.
- •ARBs did not show any impact on steroid requirements during radiotherapy in this trial. A trend towards reduction of peritumoural oedema on magnetic resonance imaging over time was seen but did not reach statistical significance.
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.
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.
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- Glioma.Nat Rev Dis Prim. 2015; 1: 15017
- Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.N Engl J Med. 2005; 352: 987-996
- Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial.J Am Med Assoc. 2015; 314: 2535-2543
- Gliomas and the vascular fragility of the blood brain barrier.Front Cell Neurosci. 2014; 8: 418
- Steroid requirements during radiotherapy for malignant gliomas.J Neuro Oncol. 2010; 100: 89-94
- Corticosteroid use in neuro-oncology: an update.Neuro Oncol Pract. 2015; 2: 6-12
- Corticosteroids compromise survival in glioblastoma.Brain. 2016; 139: 1458-1471
- VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer.Nat Rev Clin Oncol. 2009; 6: 229-236
- Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma.N Engl J Med. 2014; 370: 709-722
- Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy.J Clin Oncol. 2013; 31: 1182-1187
- Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial.Cancer. 2011; 117: 3788-3795
- Steroid-sparing effects of angiotensin-II inhibitors in glioblastoma patients.Eur J Neurol. 2012; 19: 1337-1342
- Impact of Angiotensin-II receptor blockers on vasogenic edema in glioblastoma patients.J Neurol. 2016; 263: 524-530
- Multiple angiotensin receptor subtypes in normal and tumor astrocytes in vitro.Glia. 2002; 39: 304-313
- Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma.Br J Canc. 2004; 90: 1059-1068
- Blockade of angiotensin AT1a receptor signaling reduces tumor growth, angiogenesis, and metastasis.Biochem Biophys Res Commun. 2002; 294: 441-447
- Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth.J Clin Invest. 2003; 112: 67-75
- Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma.Br J Canc. 2005; 92: 1247-1252
- AT1 receptor is present in glioma cells; its blockage reduces the growth of rat glioma.Br J Canc. 2001; 85: 1396-1399
- Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients.Cancer. 2012; 118: 4201-4211
- Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial.Oncotarget. 2016; 7: 61916-61929
- Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis.Acta Neuropathol. 2010; 119: 509-511
- Use of dexamethasone in treatment of cerebral edema associated with brain tumors.J Lancet. 1961 Feb; 81: 46-53
- Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia.Cancer Cell. 2014; 26: 605-622
- The renin-angiotensin system and malignancy.Carcinogenesis. 2008; 29: 1675-1684
- The renin-angiotensin system and cancer: old dog, new tricks.Nat Rev Canc. 2010; 10: 745-759
- Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels.Nat Commun. 2013; 4: 2516
- Inhibition of renin–angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine.Br J Canc. 2010; 103: 1644-1648
- Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy.J Canc Res Clin Oncol. 2009; 135: 1429-1435
- Effect of angiotensin system inhibitors on survival in patients receiving chemotherapy for advanced non-small-cell lung cancer.Clin Lung Canc. 2017; 18: 189-197
- Angiotensin system inhibitors and outcome of sunitinib treatment in patients with metastatic renal cell carcinoma: a retrospective examination.Eur J Cancer. 2011; 47: 1955-1961
- Hypertension and angiotensin system inhibitors: impact on outcome in sunitinib-treated patients for metastatic renal cell carcinoma.Ann Oncol. 2015; 26: 1128-1133
- Impact of renin-angiotensin system blockade on clinical outcome in glioblastoma.Eur J Neurol. 2015; 22: 1304-1309
- Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab.J Neuro Oncol. 2017; 134: 325-330
- Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?.J Neuro Oncol. 2018 Feb 8; ([Epub ahead of print])https://doi.org/10.1007/s11060-018-2786-8
- MGMT gene silencing and benefit from temozolomide in glioblastoma.N Engl J Med. 2005; 352: 997-1003
Published online: February 01, 2019
Accepted: December 23, 2018
Received in revised form: December 18, 2018
Received: October 26, 2018
© 2019 Elsevier Ltd. All rights reserved.