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Journal of Neuro-Oncology

, Volume 117, Issue 1, pp 141–145 | Cite as

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

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

Abstract

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.

Keywords

Glioblastoma Integrins Cilengitide Relapse pattern MRIcro 

Notes

Conflict of interest

The following authors disclose financial relationship with Merck KGaA (Darmstadt, Germany): Bart Neyns (research funding), Michael Weller (research funding and advisory role), Paul M Clément (payment for invited lectures and consultancy), Roger Stupp (consultancy), Jörg Tonn (advisory role and honoraria), Martin Picard (employment). Günter Eisele, Antje Wick, Anna-Carina Eisele, Ghazaleh Tabatabai, Dietmar Krex, Matthias Simon, Uwe Schlegel, Adrian Ochsenbein, Guido Nikkhah and Wolfgang Wick have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Günter Eisele
    • 1
  • Antje Wick
    • 2
  • Anna-Carina Eisele
    • 1
  • Paul M. Clément
    • 3
  • Jörg Tonn
    • 4
  • Ghazaleh Tabatabai
    • 5
  • Adrian Ochsenbein
    • 6
  • Uwe Schlegel
    • 7
  • Bart Neyns
    • 8
  • Dietmar Krex
    • 9
  • Matthias Simon
    • 10
  • Guido Nikkhah
    • 11
    • 15
  • Martin Picard
    • 12
  • Roger Stupp
    • 13
  • Wolfgang Wick
    • 2
    • 14
  • Michael Weller
    • 1
  1. 1.Department of NeurologyUniversity Hospital ZurichZurichSwitzerland
  2. 2.Department of NeurooncologyUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of OncologyKU LeuvenLouvainBelgium
  4. 4.Department of NeurosurgeryUniversity Hospital of Munich LMUMunichGermany
  5. 5.Department of General NeurologyUniversity Hospital TübingenTübingenGermany
  6. 6.Department of Medical OncologyUniversity Hospital BernBernSwitzerland
  7. 7.Department of NeurologyUniversity Hospital Bochum, Knappschaftskrankenhaus Bochum-LangendreerBochumGermany
  8. 8.Department of Medical OncologyUZ BrusselBrusselsBelgium
  9. 9.Department of NeurosurgeryUniversity Hospital Carl-Gustav Carus DresdenDresdenGermany
  10. 10.Department of NeurosurgeryUniversity Hospital BonnBonnGermany
  11. 11.Department of NeurosurgeryUniversity Hospital FreiburgFreiburgGermany
  12. 12.Merck SeronoDarmstadtGermany
  13. 13.Multidisciplinary Oncology CenterUniversity of Lausanne HospitalsLausanneSwitzerland
  14. 14.German Cancer Consortium (DKTK), Clinical Cooperation Unit NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  15. 15.Department of NeurosurgeryUniversity Hospital ErlangenErlangenGermany

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