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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-2-15
pubmed:abstractText
A number of different clinical characteristics and molecular markers related to epidermal growth factor receptor (EGFR) activation have been reported to singly correlate with therapeutic activity of EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the predictive value on gefitinib outcomes of a comprehensive panel of molecular parameters in advanced NSCLC patients. EGFR and K-ras mutations were detected by direct sequencing on tumor DNA from paraffin embedded samples. EGFR and HER2 gene copy number was assessed by FISH. EGFR protein expression was quantified by immunohistochemistry. EGFR gene intron 1 polymorphism was assessed on genomic DNA isolated from venous whole blood samples. Ninety-one patients were prospectively enrolled and the overall gefitinib response rate was 18.7% (2 complete and 15 partial responses). Sex (p=0.005), non-smoking status (p=0.010), skin toxicity (p=0.020), EGFR gene mutations (p<0.001) and EGFR FISH positivity (p=0.016) were found to be associated with gefitinib response. K-ras mutation was detected in only seven non-responder patients. The median overall survival was of 10 months. Only non-smoking status and EGFR intron 1 polymorphism showed a statistically significant correlation with survival (p=0.031 and 0.044, respectively). In conclusion, we have confirmed the role of EGFR gene mutation as predictor of response to EGFR TKIs. Moreover, EGFR gene copy number and, potentially, also EGFR intron 1 polymorphism could aid in better prediction of EGFR TKI responsiveness in advanced NSCLC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-8332
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
355-60
pubmed:meshHeading
pubmed-meshheading:19473722-Adult, pubmed-meshheading:19473722-Aged, pubmed-meshheading:19473722-Aged, 80 and over, pubmed-meshheading:19473722-Antineoplastic Agents, pubmed-meshheading:19473722-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:19473722-Female, pubmed-meshheading:19473722-Gene Dosage, pubmed-meshheading:19473722-Humans, pubmed-meshheading:19473722-Introns, pubmed-meshheading:19473722-Lung Neoplasms, pubmed-meshheading:19473722-Male, pubmed-meshheading:19473722-Middle Aged, pubmed-meshheading:19473722-Polymorphism, Genetic, pubmed-meshheading:19473722-Prognosis, pubmed-meshheading:19473722-Prospective Studies, pubmed-meshheading:19473722-Protein Kinase Inhibitors, pubmed-meshheading:19473722-Quinazolines, pubmed-meshheading:19473722-Receptor, Epidermal Growth Factor, pubmed-meshheading:19473722-Receptor, erbB-2, pubmed-meshheading:19473722-Treatment Outcome, pubmed-meshheading:19473722-Tumor Markers, Biological
pubmed:year
2010
pubmed:articleTitle
Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): study of a comprehensive panel of molecular markers.
pubmed:affiliation
Division of Medical Oncology, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy. mtiseo@ao.pr.it
pubmed:publicationType
Journal Article