Abstract | 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:
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Authors | Tobey J MacDonald, Clinton F Stewart, Mehmet Kocak, Stewart Goldman, Richard G Ellenbogen, Peter Phillips, Deborah Lafond, Tina Young Poussaint, Mark W Kieran, James M Boyett, Larry E Kun |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 26
Issue 6
Pg. 919-24
(Feb 20 2008)
ISSN: 1527-7755 [Electronic] United States |
PMID | 18281665
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- ABCB1 protein, human
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Angiogenesis Inhibitors
- Snake Venoms
- Cilengitide
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Topics |
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(genetics)
- Adolescent
- Adult
- Angiogenesis Inhibitors
(administration & dosage, adverse effects, pharmacokinetics)
- Brain Neoplasms
(drug therapy, pathology)
- Child
- Child, Preschool
- Drug Administration Schedule
- Female
- Genotype
- Humans
- Infant
- Infusions, Intravenous
- Magnetic Resonance Imaging
- Male
- Snake Venoms
(administration & dosage, adverse effects, pharmacokinetics)
- Treatment Outcome
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