Han, Ji-Youn; Kim, Jin Young; Lee, Suk Hyung; Yoo, Nam Jin; Choi, Byung Gil
Lung cancer (Amsterdam, Netherlands)
2011Nov ; 74 ( 2 ) :293-9.
PMID : 21440951
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Han, Ji-Youn -
Kim, Jin Young -
Lee, Suk Hyung -
Yoo, Nam Jin -
Choi, Byung Gil -
ABSTRACT
PURPOSE: It has been suggested that hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 are associated with gefitinib resistance in non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic roles of these proteins in NSCLC patients treated with gefitinib. PATIENTS AND
METHODS: Of 106 patients enrolled in a randomized phase II study of gefitinib, 97 had plasma samples available for ELISA testing. Of these samples, seven and eight, respectively, had HGF and IGFBP-3 values that could not be measured. Therefore, the correlations between clinical outcomes and plasma levels of HGF and IGFBP-3 were evaluated in 90 and 89 patients, respectively.
RESULTS: Plasma HGF levels were significantly higher in older patients, male patients, patients with squamous cell carcinoma, current smokers, and patients with epidermal growth factor receptor (EGFR) wild-type tumors. Low HGF levels were significantly associated with higher response rate, and longer progression-free survival (PFS) and overall survival (OS) irrespective of EGFR mutation status. In a multivariate analysis, the presence of EGFR mutations (P=0.002) and low HGF levels (P=0.031) were independently predictive of longer PFS, and an ECOG PS of 0 (P=0.001) and low HGF levels (P=0.002) were independently predictive of longer OS. No statistically significant differences were found for IGFBP-3. CONCLUSION: High HGF levels are significantly associated with resistance to gefitinib and can be used as a predictive marker for the differential outcome of gefitinib treatment in NSCLC irrespective of EGFR mutation status. CI - Copyright ??2011 Elsevier Ireland Ltd. All rights reserved.
HGF, EGFR, IGFBP3, Gefitinib, NSCLC, gefitinib (250 mg/day) or gefitinib plus simvastatin (40 mg/day)
MESH
Adult, Age Factors, Aged, Aged, 80 and over, Biomarkers, Pharmacological/blood, Carcinoma, Non-Small-Cell Lung/*diagnosis/*drug, DNA Mutational Analysis, Drug Resistance, Female, Genes, erbB-1/genetics, Hepatocyte Growth Factor/blood, Humans, Insulin-Like Growth Factor Binding Protein 3/blood, Lung Neoplasms/*diagnosis/*drug therapy/mortality/pathology/physiopathology, Male, Middle Aged, Mutation/genetics, Predictive Value of Tests, Prognosis, Quinazolines/*administration & dosage/adverse effects, Risk Factors, Sex Factors, Smoking, Survival Analysis, Treatment Outcome
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