Journal of Neuro-Oncology

, Volume 106, Issue 1, pp 147–153

Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery

  • Mark R. Gilbert
  • John Kuhn
  • Kathleen R. Lamborn
  • Frank Lieberman
  • Patrick Y. Wen
  • Minesh Mehta
  • Timothy Cloughesy
  • Andrew B. Lassman
  • Lisa M. DeAngelis
  • Susan Chang
  • Michael Prados
Clinical Study – Patient Study

Abstract

Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the αvβ3 and αvβ5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising.

Keywords

Glioblastoma Pharmacokinetics Tumor pharmacokinetics Integrins 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Mark R. Gilbert
    • 1
  • John Kuhn
    • 2
  • Kathleen R. Lamborn
    • 3
  • Frank Lieberman
    • 4
  • Patrick Y. Wen
    • 5
  • Minesh Mehta
    • 6
  • Timothy Cloughesy
    • 7
  • Andrew B. Lassman
    • 8
  • Lisa M. DeAngelis
    • 8
  • Susan Chang
    • 3
  • Michael Prados
    • 3
  1. 1.Department of Neuro-oncologyM. D. Anderson Cancer Center, The University of TexasHoustonUSA
  2. 2.The University of Texas Health Science CenterSan AntonioUSA
  3. 3.University of CaliforniaSan FranciscoUSA
  4. 4.University of PittsburghPittsburghUSA
  5. 5.Dana Farber Cancer InstituteBostonUSA
  6. 6.University of WisconsinMadisonUSA
  7. 7.University of CaliforniaLos AngelisUSA
  8. 8.Memorial Sloan-Kettering Cancer CenterNew YorkUSA

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