Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma

Roger Stupp*, Monika E. Hegi, Bart Neyns, Roland Goldbrunner, Uwe Schlegel, Paul M J Clement, Gerhard G. Grabenbauer, Adrian F. Ochsenbein, Matthias Simon, Pierre Yves Dietrich, Torsten Pietsch, Christine Hicking, Joerg Christian Tonn, Annie Claire Diserens, Alessia Pica, Mirjam Hermisson, Stefan Krueger, Martin Picard, Michael Weller

*Corresponding author for this work

Research output: Contribution to journalArticle

318 Scopus citations

Abstract

Purpose: Invasion and migration are key processes of glioblastoma and are tightly linked to tumor recurrence. Integrin inhibition using cilengitide has shown synergy with chemotherapy and radiotherapy in vitro and promising activity in recurrent glioblastoma. This multicenter, phase I/IIa study investigated the efficacy and safety of cilengitide in combination with standard chemoradiotherapy in newly diagnosed glioblastoma. Patients and Methods: Patients (age ≥ 18 to ≤ 70 years) were treated with cilengitide (500 mg) administered twice weekly intravenously in addition to standard radiotherapy with concomitant and adjuvant temozolomide. Treatment was continued until disease progression or for up to 35 weeks. The primary end point was progression-free survival (PFS) at 6 months. Results: Fifty-two patients (median age, 57 years; 62% male) were included. Six- and 12-month PFS rates were 69% (95% CI, 54% to 80%) and 33% (95% CI, 21% to 46%). Median PFS was 8 months (95% CI, 6.0 to 10.7 months). Twelve- and 24-month overall survival (OS) rates were 68% (95% CI, 53% to 79%) and 35% (95% CI, 22% to 48%). Median OS was 16.1 months (95% CI, 13.1 to 23.2 months). PFS and OS were longer in patients with tumors with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (13.4 and 23.2 months) versus those without MGMT promoter methylation (3.4 and 13.1 months). The combination of cilengitide with temozolomide and radiotherapy was well tolerated, with no additional toxicity. No pharmacokinetic interactions between temozolomide and cilengitide were identified. Conclusion: Compared with historical controls, the addition of concomitant and adjuvant cilengitide to standard chemoradiotherapy demonstrated promising activity in patients with glioblastoma with MGMT promoter methylation.

Original languageEnglish (US)
Pages (from-to)2712-2718
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number16
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma'. Together they form a unique fingerprint.

  • Cite this

    Stupp, R., Hegi, M. E., Neyns, B., Goldbrunner, R., Schlegel, U., Clement, P. M. J., Grabenbauer, G. G., Ochsenbein, A. F., Simon, M., Dietrich, P. Y., Pietsch, T., Hicking, C., Tonn, J. C., Diserens, A. C., Pica, A., Hermisson, M., Krueger, S., Picard, M., & Weller, M. (2010). Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. Journal of Clinical Oncology, 28(16), 2712-2718. https://doi.org/10.1200/JCO.2009.26.6650