Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS:
Brivanib produced enduring tumor stasis and angiogenic blockade, both first and second line following the failure of DC101 or sorafenib. Overall survival was significantly extended by brivanib versus sorafenib, both first-line and when second-line therapy was initiated prior to sorafenib failure; second-line brivanib was less beneficial when initiated later, after the initiation of revascularization and incipient tumor progression. CONCLUSIONS:
Brivanib holds promise and deserves consideration for clinical evaluation as an antiangiogenic therapy, both in the context of impending failures of VEGF-selective therapy and in a first-line setting aiming to limit the adaptive response to VEGF inhibitors that results in evasive resistance.
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Authors | Elizabeth Allen, Ian B Walters, Douglas Hanahan |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 17
Issue 16
Pg. 5299-310
(Aug 15 2011)
ISSN: 1557-3265 [Electronic] United States |
PMID | 21622725
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | ©2011 AACR. |
Chemical References |
- Antibodies, Monoclonal
- Benzenesulfonates
- DC101 monoclonal antibody
- Phenylurea Compounds
- Protein Kinase Inhibitors
- Pyridines
- Receptors, Fibroblast Growth Factor
- Triazines
- Niacinamide
- Sorafenib
- brivanib
- Vascular Endothelial Growth Factor Receptor-2
- Alanine
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Topics |
- Alanine
(administration & dosage, analogs & derivatives, pharmacology)
- Animals
- Antibodies, Monoclonal
(administration & dosage, pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Benzenesulfonates
(administration & dosage, pharmacology)
- Blotting, Western
- Drug Resistance, Neoplasm
(drug effects)
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Mice
- Mice, Knockout
- Mice, Transgenic
- Neuroendocrine Tumors
(drug therapy, genetics, metabolism)
- Niacinamide
(analogs & derivatives)
- Pancreatic Neoplasms
(drug therapy, genetics, metabolism)
- Phenylurea Compounds
- Protein Kinase Inhibitors
(pharmacology)
- Pyridines
(administration & dosage, pharmacology)
- Receptors, Fibroblast Growth Factor
(antagonists & inhibitors, metabolism)
- Sorafenib
- Treatment Outcome
- Triazines
(administration & dosage, pharmacology)
- Tumor Burden
(drug effects)
- Vascular Endothelial Growth Factor Receptor-2
(antagonists & inhibitors, metabolism)
|