Linked Life Data

12853203

Source:http://linkedlifedata.com/resource/pubmed/id/12853203

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9377
pubmed:dateCreated
2003-7-10
pubmed:abstractText
CONTEXT: Aberrant signalling through the epidermal growth factor receptor (EGFR) is associated with neoplastic cell proliferation, migration, stromal invasion, resistance to apoptosis, and angiogenesis. The high frequency of abnormalities in EGFR signalling in human carcinomas and gliomas and laboratory studies showing that inhibition of EGFRcan impair tumour growth means that EGFR is an attractive target for the development of cancer therapeutics. Among the classes of agents targeting EGFR in clinical development are monoclonal antibodies against the extracellular ligand-binding domain of the receptor, and small molecules that inhibit activation of the receptor tyrosine kinase. Although there are pharmacological and mechanistic differences between the two classes of inhibitor, preclinical studies suggest they both inhibit cell proliferation and have additive or synergistic cytotoxicity with standard therapies. Results from early clinical trials indicate that these agents are well tolerated and have anti-tumour activity. STARTING POINT: In May, 2003, the Australian Therapeutic Goods Administration and the US Food and Drug Administration approved the EGFR inhibitor gefitinib (ZD1839, Iressa) for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. The US approval was based on results of a phase 2 study of 216 patients with NSCLC, including 142 patients with refractory disease. In this subgroup, the response rate was about 10%. The approval of the drug was granted despite negative results from two randomised controlled trials in over 2000 previously untreated patients with NSCLC, which showed no benefit in survival, objective tumour response, or time to progression when gefitinib was added to chemotherapy. WHERE NEXT? Research is needed to identify and validate predictive factors that can be used to select patients with disease likely to respond to EGFR inhibitors, and to elucidate the mechanism of interaction of these agents with standard therapies and other molecularly targeted agents. Appropriately designed clinical trials are required to define the optimum dose, schedule, and sequence for these agents in combination with conventional therapies and other targeted agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1474-547X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
362
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Targeting epidermal growth factor receptor--are we missing the mark?
pubmed:affiliation
Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Review