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

  • Clinical Study – Patient Study
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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.

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Acknowledgments

The Cilengitide was generously provided by Merck KgaA and the National Cancer Institute, NIH. This study was sponsored by NIH Grant U01 CA-062412.

Conflict of interest

Mark R. Gilbert, MD: Research support from Genentech, Advisory Affiliations with Merck, Genentech.

John Kuhn, Pharm D., Kathleen R. Lamborn, PhD, Patrick Y. Wen, MD, Timothy Cloughesy, MD, Lisa M. DeAngelis, MD, Susan Chang, MD, and Michael Prados, MD: None.

Frank Lieberman, MD: Advisory affiliations with Roche/Genentech. Paid consulting with Roche/Genentech and EMD Merck.

Minesh Mehta, MD: Consultant to Adnexus, Bayer, Genenteh, Merck, Schering Plough, YM BioSciences and Tomotherapy; on the Board of Directors of Pharmacyclics, an advisor to Colby and Stemina, and is on the DSMB for Apogenix. He holds stock options in Pharmacyclics and Tomotherapy.

Andrew B. Lassman, MD: Research support from Schering Plough, Sigma Tau, Genentech, Keryx, Astra Zeneca, Exelixis. Advisory affiliations with Bristol-Myers Squibb, Campus Bio, Cephalon, Eisai, Enzon, Genentech, Imclone, Schering-Plough, Merck. Paid consulting with Schering Plough, Merck.

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Authors and Affiliations

  1. Department of Neuro-oncology, M. D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Mark R. Gilbert

  2. The University of Texas Health Science Center, San Antonio, TX, USA

    John Kuhn

  3. University of California, San Francisco, CA, USA

    Kathleen R. Lamborn, Susan Chang & Michael Prados

  4. University of Pittsburgh, Pittsburgh, PA, USA

    Frank Lieberman

  5. Dana Farber Cancer Institute, Boston, MA, USA

    Patrick Y. Wen

  6. University of Wisconsin, Madison, WI, USA

    Minesh Mehta

  7. University of California, Los Angelis, CA, USA

    Timothy Cloughesy

  8. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Andrew B. Lassman & Lisa M. DeAngelis

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  1. Mark R. Gilbert
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  2. John Kuhn
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  3. Kathleen R. Lamborn
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  9. Lisa M. DeAngelis
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  10. Susan Chang
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  11. Michael Prados
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Correspondence to Mark R. Gilbert.

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Gilbert, M.R., Kuhn, J., Lamborn, K.R. et al. Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery. J Neurooncol 106, 147–153 (2012). https://doi.org/10.1007/s11060-011-0650-1

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  • DOI: https://doi.org/10.1007/s11060-011-0650-1

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