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Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

Eisele, Günter ; Wick, Antje ; Eisele, Anna-Carina ; Clément, Paul ; Tonn, Jörg ; Tabatabai, Ghazaleh ; Ochsenbein, Adrian ; Schlegel, Uwe ; Neyns, Bart ; Krex, Dietmar ; Simon, Matthias ; Nikkhah, Guido ; Picard, Martin ; Stupp, Roger ; Wick, Wolfgang ; Weller, Michael

In: Journal of Neuro-Oncology, 2014, vol. 117, no. 1, p. 141-145

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    Titre
    • Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression
    Auteur
    • Eisele, Günter. Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland
    • Wick, Antje. Department of Neurooncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 68120, Heidelberg, Germany
    • Eisele, Anna-Carina. Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland
    • Clément, Paul. Department of Oncology, KU Leuven, Herestraat 49, 3000, Louvain, Belgium
    • Tonn, Jörg. Department of Neurosurgery, University Hospital of Munich LMU, Marchioninistrasse 15, 81377, Munich, Germany
    • Tabatabai, Ghazaleh. Department of General Neurology, University Hospital Tübingen, Hoppe-Seyler Strasse 3, 72076, Tübingen, Germany
    • Ochsenbein, Adrian. Department of Medical Oncology, University Hospital Bern, Freiburgstrasse 4, 3010, Bern, Switzerland
    • Schlegel, Uwe. Department of Neurology, University Hospital Bochum, Knappschaftskrankenhaus Bochum-Langendreer, In der Schonau 23-25, 44892, Bochum, Germany
    • Neyns, Bart. Department of Medical Oncology, UZ Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
    • Krex, Dietmar. Department of Neurosurgery, University Hospital Carl-Gustav Carus Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
    • Simon, Matthias. Department of Neurosurgery, University Hospital Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany
    • Nikkhah, Guido. Department of Neurosurgery, University Hospital Freiburg, Breisacher Strasse 64, 79106, Freiburg, Germany
    • Picard, Martin. Merck Serono, Alsfelder Strasse 17, 64289, Darmstadt, Germany
    • Stupp, Roger. Multidisciplinary Oncology Center, University of Lausanne Hospitals, 46 Rue du Bugnon, 1011, Lausanne, Switzerland
    • Wick, Wolfgang. Department of Neurooncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 68120, Heidelberg, Germany
    • Weller, Michael. Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Journal of Neuro-Oncology, 2014, vol. 117, no. 1, p. 141-145. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:325810
    Summary
    The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT→TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT→TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O6-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20% in the reference group and 19% (4/21 patients) in the cilengitide group. Compared with TMZ/RT→TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma.