PURPOSE: A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors. PATIENTS AND METHODS: Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m(2). Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients. RESULTS: No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m(2) experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m(2), the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m(2). Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months. CONCLUSION: The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m(2). A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group.
PURPOSE: A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors. PATIENTS AND METHODS: Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m(2). Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients. RESULTS: No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m(2) experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m(2), the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m(2). Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months. CONCLUSION: The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m(2). A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group.
Authors: Deborah A Bradley; Stephanie Daignault; Charles J Ryan; Robert S Dipaola; Kathleen A Cooney; David C Smith; Eric Small; Paul Mathew; Mitchell E Gross; Mark N Stein; Alice Chen; Kenneth J Pienta; June Escara-Wilke; Gerald Doyle; Mahmoud Al-Hawary; Evan T Keller; Maha Hussain Journal: Invest New Drugs Date: 2010-03-25 Impact factor: 3.850
Authors: Ulrike Löbel; Jan Sedlacik; Noah D Sabin; Mehmet Kocak; Alberto Broniscer; Claudia M Hillenbrand; Zoltán Patay Journal: Neuroradiology Date: 2010-09-28 Impact factor: 2.804