Assessment of the biological and pharmacological effects of the αvβ3 and αv β5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors

S. Hariharan, D. Gustafson, S. Holden, D. McConkey, D. Davis, M. Morrow, M. Basche, L. Gore, C. Zang, C. L. O'Bryant, A. Baron, D. Gallemann, D. Colevas, S. Gail Eckhardt

Research output: Contribution to journalArticlepeer-review


Background: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins αvβ3 and αvβ5 to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. Patients and methods: The doses of cilengitide were 600 or 1200 mg/m2 as a 1-h infusion twice weekly every 28 days. A novel dose escalation scheme was utilized that relied upon the biological activity rate. Results: Twenty patients received 50 courses of cilengitide with no dose-limiting toxic effects. The pharmacokinetic (PK) profile revealed a short elimination half-life of 4 h, supporting twice weekly dosing. Of the six soluble angiogenic molecules assessed, only E-selectin increased significantly from baseline. Analysis of tumor microvessel density and gene expression was not informative due to intrapatient tumor heterogeneity. Although several patients with evaluable tumor biopsy pairs did reveal posttreatment increases in tumor and endothelial cell apoptosis, these results did not reach statistical significance due to the aforementioned heterogeneity. Conclusions: Cilengitide is a well-tolerated antiangiogenic agent. The biomarkers chosen in this study underscore the difficulty in assessing the biological activity of antiangiogenic agents in the absence of validated biological assays.

Original languageEnglish (US)
Pages (from-to)1400-1407
Number of pages8
JournalAnnals of Oncology
Issue number8
StatePublished - Aug 2007
Externally publishedYes


  • Angiogenesis
  • Cilengitide
  • Integrins
  • Phase I trials

ASJC Scopus subject areas

  • Hematology
  • Oncology


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