A phase I study of ABT-510 plus bevacizumab in advanced solid tumors.
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 articleSubject
ABT-510advanced 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
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https://hdl.handle.net/10161/11086Published Version (Please cite this version)
10.1002/cam4.65Publication 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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Show full item recordScholars@Duke
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
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 adoptive
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
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
Hope Elizabeth Uronis
Associate Professor of Medicine
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