Steroid-sparing effects of angiotensin-II inhibitors in glioblastoma patients.
BACKGROUND
The standard of care in patients with glioblastoma (GBM) relies on surgical resection, radiation therapy (RT), and temozolomide. Steroids are required in almost all patients to reduce peritumoral edema, but are associated with numerous side effects. Vascular endothelial growth factor (VEGF) is a key driver of peritumoral edema and angiogenesis in human GBM. Recently, angiotensin-II inhibitors were reported to reduce VEGF secretion and tumor growth in some animal models.


METHODS
To investigate whether angiotensin-II inhibitors might have a similar effect in humans and before undertaking a prospective study, we retrospectively investigated a series of 87 consecutive, newly diagnosed GBM patients, treated in a single center. Amongst these patients, 29 (33%) were already treated before RT for high blood pressure (HBP), 18 of them (21%) with an angiotensin-II inhibitor. In all patients, performance status, surgical procedures, and steroid dosages were documented.


RESULTS
Patients treated with angiotensin-II inhibitors, but not other antihypertensive drugs, required half of the steroids of the other patients during radiotherapy (P = 0.005 in multivariate analysis, considering other antihypertensive treatments, surgical resection, and performance status). This effect of angiotensin-II inhibitors was also significant at the beginning of radiotherapy (P = 0.03 in multivariate analysis). Treatment with angiotensin-II inhibitors had no effect on survival (16.2 vs. 17.9 months for the treated and the non-treated group, respectively, P = 0.77).


CONCLUSIONS
Angiotensin-II inhibitors might display significant steroid-sparing effects in brain tumor patients. Given the morbidity associated with steroids, this finding might have important practical consequences in these patients and warrants a randomized study.
Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service de Neurologie, Bobigny, France. antoine.carpentier@avc.aphp.fr
A F
AF
Carpentier
D
D
Ferrari
O
O
Bailon
R
R
Ursu
C
C
Banissi
A-L
AL
Dubessy
C
C
Belin
C
C
Levy
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D001932:Brain Neoplasms / Q000188:drug therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II