Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-53281
Salazar, F; Molina, M A; Sanchez-Ronco, M; Moran, T; Ramirez, J L; Sanchez, J M; Stahel, R; Garrido, P; Cobo, M; Isla, D; Bertran-Alamillo, J; Massuti, B; Cardenal, F; Manegold, C; Lianes, P; Trigo, J M; Sanchez, J J; Taron, M; Rosell, R (2011). 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. Lung Cancer, 72(1):84-91.
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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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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology|
|DDC:||610 Medicine & health|
|Deposited On:||07 Jan 2012 21:14|
|Last Modified:||01 Dec 2013 16:50|
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