Phase I/IIa Study of Cilengitide and Temozolomide With Concomitant Radiotherapy Followed by Cilengitide and Temozolomide Maintenance Therapy in Patients With Newly Diagnosed Glioblastoma

American Society of Clinical Oncology (ASCO) - Tập 28 Số 16 - Trang 2712-2718 - 2010
Roger Stupp1, Monika E. Hegi1, Bart Neyns1, Roland Goldbrunner1, Uwe Schlegel1, Paul M. Clément1, Gerhard G. Grabenbauer1, Adrian F. Ochsenbein1, Matthias Simon1, Pierre-Yves Dietrich1, Torsten Pietsch1, Christine Hicking1, Joerg C. Tonn1, Annie-Claire Diserens1, Alessia Pica1, Mirjam Hermisson1, Stefan Krueger1, Martin Picard1, Michael Weller1
1From the Centre Pluridisciplinaire d'Oncologie, Department of Neurosurgery, Service de Radio-Oncologie, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne; Institute of Medical Oncology, University of Bern, Bern; Division d'Oncologie, Hôpitaux Universitaires de Genève, Geneva; Department of Neurology, University Hospital, Zurich, Switzerland; Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels; Department of Clinical Oncology, Katholieke Universiteit...

Tóm tắt

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.

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Thông tin xuất bản

American Society of Clinical Oncology (ASCO)

Tập 28 Số 16

2712-2718

Thông tin tác giả