• L Burt Nabors, Karen L Fink, Tom Mikkelsen, Danica Grujicic, Rafal Tarnawski, Do Hyun Nam, Maria Mazurkiewicz, Michael Salacz, Lynn Ashby, Vittorina Zagonel, Roberta Depenni, James R Perry, Christine Hicking, Martin Picard, Monika E Hegi, Benoit Lhermitte, and David A Reardon.
• University of Alabama at Birmingham, Birmingham, Alabama (L.B.N.); Baylor University Medical Center, Dallas, Texas (K.L.F.); Henry Ford Hospital, Detroit, Michigan (T.M.); Clinic for Neurosurgery, Clinical Center of Serbia, Medical Faculty University of Belgrade, Belgrade, Serbia (D.G.); Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, Radiotherapy and Chemotherapy Clinic, Gliwice, Poland (R.T.); Samsung Medical Center, Seoul, South Korea (D.H.N.); Centrum Onkologii Ziemi Lubelskiej, Lublin, Poland (M.M.); St. Luke's Brain Tumor Center, St. Luke's Hospital, Kansas City, Missouri (M.S.); Barrow Neurological Institute, Phoenix, Arizona (L.A.); Medical Oncology Unit 1, IOV, IRCCS, Padova, Italy (V.Z.); Policlinico di Modena, Modena, Italy (R.D.); Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Merck KGaA, Darmstadt, Germany (C.H., M.P.); Department of Clinical Neurosciences, University Hospital Lausanne, Lausanne, Switzerland (M.E.H.); Institute of Pathology, University Hospital Lausanne, Lausanne, Switzerland (B.L.); Dana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.).
• Neuro-oncology. 2015 May 1; 17 (5): 708-17.

BackgroundSurvival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter.MethodsOverall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability.ResultsMedian overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated.ConclusionsStandard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

41 keywords...

hide…