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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-35461

Stupp, R; Hegi, M E; Neyns, B; Goldbrunner, R; Schlegel, U; Clement, P M; 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.

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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 > or = 18 to < or = 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 O(6)-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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:2010
Deposited On:17 Aug 2010 11:10
Last Modified:17 Jul 2014 10:23
Publisher:American Society of Clinical Oncology
ISSN:0732-183X
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1200/JCO.2009.26.6650
PubMed ID:20439646
Citations:Web of Science®. Times Cited: 152
Google Scholar™
Scopus®. Citation Count: 176

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