Document Detail


Lessons from phase III clinical trials on anti-VEGF therapy for cancer.
MedLine Citation:
PMID:  16407877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In randomized phase III trials two anti-vascular endothelial growth factor (VEGF) approaches have yielded survival benefit in patients with metastatic cancer. In one approach, the addition of bevacizumab, a VEGF-specific antibody, to standard chemotherapy improved overall survival in colorectal and lung cancer patients and progression-free survival in breast cancer patients. In the second approach, multitargeted tyrosine kinase inhibitors that block VEGF receptor and other kinases in both endothelial and cancer cells, demonstrated survival benefit in gastrointestinal stromal tumor and renal-cell-carcinoma patients. By contrast, adding bevacizumab to chemotherapy failed to increase survival in patients with previously treated and refractory metastatic breast cancer. Furthermore, addition of vatalanib, a kinase inhibitor developed as a VEGF receptor-selective agent, to chemotherapy did not show a similar benefit in metastatic colorectal cancer patients. These contrasting responses raise critical questions about how these agents work and how to combine them optimally. We summarize three of the many potential mechanisms of action of anti-VEGF agents, and also discuss progress relating to the identification of potential biomarkers for anti-VEGF-agent efficacy in humans.
Authors:
Rakesh K Jain; Dan G Duda; Jeffrey W Clark; Jay S Loeffler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Nature clinical practice. Oncology     Volume:  3     ISSN:  1743-4254     ISO Abbreviation:  Nat Clin Pract Oncol     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-12     Completed Date:  2006-05-02     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  101226509     Medline TA:  Nat Clin Pract Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  24-40     Citation Subset:  IM    
Affiliation:
Department of Radiation Oncology, Harvard Medical School, and Massachusetts General Hospital, Boston, MA 02114, USA. jain@steele.mgh.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / therapeutic use*
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
Antineoplastic Agents / pharmacology,  therapeutic use*
Clinical Trials, Phase III as Topic*
Humans
Neoplasms / drug therapy*
Neovascularization, Pathologic / drug therapy*
Protein-Tyrosine Kinases / antagonists & inhibitors
Tumor Markers, Biological
Vascular Endothelial Growth Factors / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents; 0/Tumor Markers, Biological; 0/Vascular Endothelial Growth Factors; 2S9ZZM9Q9V/bevacizumab; EC 2.7.10.1/Protein-Tyrosine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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