title: Adverse event grading following CTCAE v3.0 underestimates hypertensive side effects in patients with glioma treated with Bevacizumab.
abstract: Anti-VEGF therapy with Bevacizumab (BEV) is widely used in cases of relapsed high-grade glioma (HGG). Arterial hypertension is a known side effect of anti-VEGF therapy. 42 Patients with relapsed HGG were treated with BEV 10 mg/kg on days 1 and 15 of 28-day cycles in addition to treatment with 40 mg TMZ daily until disease progression, based on magnetic resonance imaging and/or worsening of clinical status. In a retrospective analysis, hypertensive side effects were evaluated as the primary endpoint, while survival information in addition to toxicity was analyzed as secondary endpoint. Grading which employs the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 detected hypertensive events with a significantly higher sensitivity than CTCAE version 3.0. The rate of severe hypertensive events observed as CTCAE ≥ °3 were 9.5 % in version 3.0 and 45.2 % in version 4.0. The results presented here indicate that CTCAE version 3.0 may underreport the incidence and grade of BEV-induced hypertension within clinical trials. As hypertension has not only long-term, but also severe short-term side effects, we suggest that arterial hypertension under BEV should be scored according to CTCAE version 4.0 to avoid clinically relevant hypertension-related adverse events in these patients.
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Universitätsstraße 84, 93053, Regensburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bumes
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Universitätsstraße 84, 93053, Regensburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rzonsa
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Universitätsstraße 84, 93053, Regensburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hutterer
authors.affiliation: Department of Neurosurgery, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Universitätsstraße 84, 93053, Regensburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.affiliation: Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Riemenschneider
authors.affiliation: Department of Neurology, University of Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Uhl
authors.affiliation: Department of Radiology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Wendl
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Universitätsstraße 84, 93053, Regensburg, Germany. peter.hau@ukr.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000068258:Bevacizumab / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
keywords: Bevacizumab; CTCAE; Glioblastoma; High-grade glioma; Hypertension; Temozolomide