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.