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Adverse event grading following CTCAE v3.0 underestimates hypertensive side effects in patients with glioma treated with Bevacizumab

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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.

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    Authors and Affiliations

    1. Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Universitätsstraße 84, 93053, Regensburg, Germany

      Elisabeth Bumes, Sarah Rzonsa, Markus Hutterer, Ulrich Bogdahn & Peter Hau

    2. Department of Neurosurgery, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

      Martin Proescholdt

    3. Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

      Markus J. Riemenschneider

    4. Department of Radiology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

      Christina Wendl

    5. Department of Neurology, University of Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany

      Martin Uhl

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    1. Elisabeth Bumes
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    Correspondence to Peter Hau.

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    The authors declare that they have no competing interests. None of the authors received any funding support for this work. Peter Hau, Markus Hutterer, Martin Proescholdt and Martin Uhl have served as scientific consultants for Roche Pharma AG, Germany, and have received honoraria from Roches speakers bureau.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study (retrospective analysis) formal consent is not required.

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    Elisabeth Bumes and Sarah Rzonsa have equally contributed to this work.

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    Bumes, E., Rzonsa, S., Hutterer, M. et al. Adverse event grading following CTCAE v3.0 underestimates hypertensive side effects in patients with glioma treated with Bevacizumab. J Neurooncol 127, 191–200 (2016). https://doi.org/10.1007/s11060-015-2031-7

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