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

Eisele, Günter; Wick, Antje; Eisele, Anna-Carina; Clément, Paul M; Tonn, Jörg; Tabatabai, Ghazaleh; Ochsenbein, Adrian; Schlegel, Uwe; Neyns, Bart; Krex, Dietmar; Langenegger, Simon Matthias; Nikkhah, Guido; Picard, Martin; Stupp, Roger; Wick, Wolfgang; Weller, Michael (2014). Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. Journal of neuro-oncology, 117(1), pp. 141-145. Springer 10.1007/s11060-014-1365-x

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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 O(6)-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

UniBE Contributor:

Ochsenbein, Adrian and Langenegger, Simon Matthias

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health

ISSN:

0167-594X

Publisher:

Springer

Language:

English

Submitter:

Monique Ryter

Date Deposited:

09 Feb 2015 08:14

Last Modified:

27 Aug 2015 10:47

Publisher DOI:

10.1007/s11060-014-1365-x

PubMed ID:

24442484

BORIS DOI:

10.7892/boris.62852

URI:

https://boris.unibe.ch/id/eprint/62852

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