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rdf:type |
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lifeskim:mentions |
umls-concept:C0013216,
umls-concept:C0025723,
umls-concept:C0087111,
umls-concept:C0229671,
umls-concept:C0441772,
umls-concept:C0449438,
umls-concept:C0684249,
umls-concept:C1274040,
umls-concept:C1426948,
umls-concept:C1443775,
umls-concept:C1516213,
umls-concept:C1708063
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pubmed:issue |
1
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pubmed:dateCreated |
2011-3-7
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pubmed:abstractText |
The potential differential effect of first-line treatment and molecular mechanisms on survival to second-line chemotherapy or EGFR tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) has not been fully investigated. In particular, CHFR is frequently methylated in NSCLC and may influence outcome. We analyzed the outcome of second-line chemotherapy or EGFR TKIs in 179 of 366 patients who had been treated in an ERCC1 mRNA-based customized cisplatin trial and correlated the results with CHFR methylation status. CHFR methylation in circulating DNA was examined by methylation-specific assay. A panel of seven human EGFR wild-type NSCLC cell lines was characterized for their sensitivity to sequential treatment with cisplatin and erlotinib, and the results were correlated with CHFR. Patients who had received first-line docetaxel/cisplatin attained an overall survival of 19.2 months when treated with second-line EGFR TKIs, in comparison with 10.7 months when treated with second-line chemotherapy (P = 0.0002). However, for patients who had received first-line docetaxel/gemcitabine, overall survival was 14.8 months with EGFR TKIs and 10.8 months with chemotherapy (P = 0.29). For patients with unmethylated CHFR overall survival to EGFR TKIs was 21.4 months, and 11.2 months for those with treated with chemotherapy (P = 0.0001). In the only lung tumor cell line not expressing CHFR, pretreatment with cisplatin was antagonistic to erlotinib, while it was synergistic in the other six lines. Second-line EGFR TKIs improved survival in patients receiving first-line cisplatin-based treatment. Unmethylated CHFR predicts increased survival to EGFR TKIs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CHFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/erlotinib
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1872-8332
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pubmed:author |
pubmed-author:Bertran-AlamilloJordiJ,
pubmed-author:CardenalFelipeF,
pubmed-author:CoboManuelM,
pubmed-author:GarridoPilarP,
pubmed-author:IslaDoloresD,
pubmed-author:LianesPilarP,
pubmed-author:ManegoldChristianC,
pubmed-author:MassutiBartomeuB,
pubmed-author:MolinaMiguel AngelMA,
pubmed-author:MoranTeresaT,
pubmed-author:RamirezJose LuisJL,
pubmed-author:RosellRafaelR,
pubmed-author:SalazarFernandaF,
pubmed-author:Sanchez-RoncoMariaM,
pubmed-author:SanchezJose JavierJJ,
pubmed-author:SanchezJose MiguelJM,
pubmed-author:StahelRolfR,
pubmed-author:TaronMiquelM,
pubmed-author:TrigoJose ManuelJM
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
84-91
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pubmed:meshHeading |
pubmed-meshheading:20705357-Adult,
pubmed-meshheading:20705357-Aged,
pubmed-meshheading:20705357-Antineoplastic Agents,
pubmed-meshheading:20705357-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:20705357-Cell Cycle Proteins,
pubmed-meshheading:20705357-Cell Line, Tumor,
pubmed-meshheading:20705357-Cell Proliferation,
pubmed-meshheading:20705357-Cisplatin,
pubmed-meshheading:20705357-Female,
pubmed-meshheading:20705357-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20705357-Genes, ras,
pubmed-meshheading:20705357-Humans,
pubmed-meshheading:20705357-Lung Neoplasms,
pubmed-meshheading:20705357-Male,
pubmed-meshheading:20705357-Methylation,
pubmed-meshheading:20705357-Middle Aged,
pubmed-meshheading:20705357-Mutation,
pubmed-meshheading:20705357-Neoplasm Proteins,
pubmed-meshheading:20705357-Neoplasm Staging,
pubmed-meshheading:20705357-Protein Kinase Inhibitors,
pubmed-meshheading:20705357-Quinazolines,
pubmed-meshheading:20705357-Receptor, Epidermal Growth Factor,
pubmed-meshheading:20705357-Survival Analysis
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pubmed:year |
2011
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pubmed:articleTitle |
First-line therapy and methylation status of CHFR in serum influence outcome to chemotherapy versus EGFR tyrosine kinase inhibitors as second-line therapy in stage IV non-small-cell lung cancer patients.
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pubmed:affiliation |
Catalan Institute of Oncology, Badalona, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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