Linked Life Data

17470689

Source:http://linkedlifedata.com/resource/pubmed/id/17470689

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-5-1
pubmed:abstractText
Clinical trials showing longer survival when chemotherapy is combined with antiangiogenic agents (AAs) have led to growing interest in designing combined modality protocols that exploit abnormalities in tumor vasculature. Approved agents include bevacizumab, a recombinant monoclonal antibody that binds to vascular endothelial growth factor, and two small molecule multitargeted tyrosine kinase inhibitors of angiogenesis (SU11248 and BAY-43-9006) that have been approved for therapy of renal cancer. Targeting tumor vasculature has a strong biological rationale in radiation therapy, and preclinical studies consistently show an increase in radiosensitization with combined treatment. Preclinical studies indicate that excessive damage to tumor vasculature can result in radioresistance in some situations, and early clinical data suggest that treatment sequencing may be important when combining AAs with radiation. Radiation itself appears to antagonize any hypoxia that can be induced by long-term administration of AAs. The optimal biological doses of AAs with radiotherapy are unknown, and surrogate markers of efficacy remain to be validated. Early clinical trials should therefore include studies designed to identify mechanisms of interaction and increases in tumor hypoxia. This review highlights preclinical and early clinical data that are relevant for clinical trial design. Optimal radiation planning and delivery is required to minimize the volume of irradiated normal organs and to establish safe dose-volume parameters for phase II-III clinical trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized, http://linkedlifedata.com/resource/pubmed/chemical/Benzenesulfonates, http://linkedlifedata.com/resource/pubmed/chemical/Indoles, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A, http://linkedlifedata.com/resource/pubmed/chemical/bevacizumab, http://linkedlifedata.com/resource/pubmed/chemical/raf Kinases, http://linkedlifedata.com/resource/pubmed/chemical/sorafenib, http://linkedlifedata.com/resource/pubmed/chemical/sunitinib
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1083-7159
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
465-77
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Design of clinical trials of radiation combined with antiangiogenic therapy.
pubmed:affiliation
Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands. s.senan@vumc.nl
pubmed:publicationType
Journal Article, Review