Originally published as JCO Early Release 10.1200/JCO.2008.16.7510 on November 3 2008

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Randomized Phase II Study of Cilengitide, an Integrin-Targeting Arginine-Glycine-Aspartic Acid Peptide, in Recurrent Glioblastoma Multiforme

David A. Reardon, Karen L. Fink, Tom Mikkelsen, Timothy F. Cloughesy, Alison O'Neill, Scott Plotkin, Michael Glantz, Paula Ravin, Jeffrey J. Raizer, Keith M. Rich, David Schiff, William R. Shapiro, Susan Burdette-Radoux, Edward J. Dropcho, Sabine M. Wittemer, Johannes Nippgen, Martin Picard, L. Burt Nabors

From the Duke University Medical Center, Durham, NC; Baylor University Medical Center, Dallas, TX; Henry Ford Hospital, Detroit, MI; University of California, Los Angeles Medical Center, Los Angeles, CA; TransMolecular, Inc, Cambridge; Massachusetts General Hospital, Boston; University of Massachusetts Medical Center, Worcester, MA; Northwestern University Medical Center, Chicago, IL; Washington University, St Louis, MO; University of Virginia Health Science Center, Charlottesville, VA; Barrow Neurological Institute, Phoenix, AZ; University of Vermont, Burlington, VT; Indiana University Medical Center, Indianapolis, IN; University of Alabama at Birmingham, Birmingham, AL; and Merck KGaA Pharmaceuticals, Darmstadt, Germany.

Corresponding author: David A. Reardon, MD, The Brain Tumor Center at Duke, Duke University Medical Center, Box 3624, Durham, NC 27710; e-mail: reard003{at}mc.duke.edu

Purpose Cilengitide, an inhibitor of vβ3 and vβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence.

Patients and Methods Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments.

Results Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months.

Conclusion Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.

published online ahead of print at www.jco.org on November 3, 2008.

Supported by a grant from Merck KGaA and its affiliate EMD Pharmaceuticals.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Cilengitide: Does It Really Represent a New Targeted Therapy for Recurrent Glioblastoma?
  Marc C. Chamberlain
  JCO 2009 27: 1921 [Full Text]

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