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A phase I study of ABT-510 plus bevacizumab in advanced solid tumors.

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Date
2013-06
Authors
Uronis, Hope E
Cushman, Stephanie M
Bendell, Johanna C
Blobe, Gerard C
Morse, Michael A
Nixon, Andrew B
Dellinger, Andrew
Starr, Mark D
Li, Haiyan
Meadows, Kellen
Gockerman, Jon
Pang, Herbert
Hurwitz, Herbert I
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(13 total)
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Abstract
Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT-510 in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. Thirty-four evaluable subjects were enrolled and received study drug. Therapy was well tolerated; minimal treatment-related grade 3/4 toxicity was observed. One patient treated at dose level 1 had a partial response and five other patients treated at the recommended phase II dose had prolonged stable disease for more than 1 year. Biomarker evaluation revealed increased levels of D-dimer, von Willebrand factor, placental growth factor, and stromal-derived factor 1 in response to treatment with the combination of bevacizumab and ABT-510. Data suggest that continued evaluation of combination antiangiogenesis therapies may be clinically useful.
Type
Journal article
Subject
ABT-510
advanced solid tumors
bevacizumab
phase I
Adult
Aged
Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Dose-Response Relationship, Drug
Female
Humans
Male
Middle Aged
Neoplasms
Oligopeptides
Young Adult
Permalink
https://hdl.handle.net/10161/11086
Published Version (Please cite this version)
10.1002/cam4.65
Publication Info
Uronis, Hope E; Cushman, Stephanie M; Bendell, Johanna C; Blobe, Gerard C; Morse, Michael A; Nixon, Andrew B; ... Hurwitz, Herbert I (2013). A phase I study of ABT-510 plus bevacizumab in advanced solid tumors. Cancer Med, 2(3). pp. 316-324. 10.1002/cam4.65. Retrieved from https://hdl.handle.net/10161/11086.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Blobe

Gerard Conrad Blobe

Professor of Medicine
Our laboratory focuses on transforming growth factor-ß (TGF-ß) superfamily signal transduction pathways, and specifically, the role of these pathways in cancer biology. The TGF-ß superfamily is comprised of a number of polypeptide growth factors, including TGF-βs, bone morphogenetic proteins (BMPs) and activin) that regulate growth, differentiation and morphogenesis in a cell and context specific manner. TGF-ß and the TGF-ß signaling pathway have a dichotomo
Morse

Michael Aaron Morse

Professor of Medicine
We are studying the use of immune therapies to treat various cancers, including gastrointestinal, breast, and lung cancers and melanoma. These therapies include vaccines based on dendritic cells developed in our laboratory as well as vaccines based on peptides, viral vectors, and DNA plasmids. Our group is also a national leader in the development and use of laboratory assays for demonstrating immunologic responses to cancer vaccines. Finally, we are developing immunotherapies based on ado
Nixon

Andrew Benjamin Nixon

Professor in Medicine
Andrew Nixon, PhD, MBA (Professor of Medicine) is Director of the Phase I Biomarker Laboratory, which brings together clinical, translational and basic research to pursue the development of novel biomarkers defining mechanisms of sensitivity, resistance, and toxicity to given therapeutic drug classes, particularly anti-angiogenic agents. Additionally, the laboratory has been appointed as a Molecular Reference Laboratory for the Alliance oncology cooperative group, a national clinical trial resea
Pang

Herbert Pang

Adjunct Assistant Professor in the Department of Biostatistics & Bioinformatics
Classification and Predictive Models Design and Analysis of Biomarker Clinical Trials Genomics Pathway Analysis
Uronis

Hope Elizabeth Uronis

Associate Professor of Medicine
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