Abstract
BackgroundGefitinib, an EGFR-tyrosine kinase inhibitor, significantly improve prognosis in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the usefulness of MUC1 and vascular endothelial growth factor (VEGF) mRNA expression in peripheral blood as means of predicting benefit from gefitinib therapy in NSCLC patients.MethodsMUC1 and VEGF mRNA expressions were detected in peripheral blood of 66 patients with advanced NSCLC before (B0) and 4 weeks after treatment (B4w) with gefitinib, using real-time quantitative-PCR assay. Correlations between blood MUC1 and VEGF mRNA expression at B0 and B4w and the response to gefitinib treatment and survival were analyzed.ResultsBlood levels of MUC1 and VEGF mRNA at B0 and at B4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. Furthermore, blood MUC1 and VEGF mRNA positivity at two time points were strongly associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0.005 and P = 0.008 at B0, and P < 0.001 and P = 0.001 at B4w, respectively, for MUC1; P = 0.004 and P = 0.009 at B0, and P = 0.001 and P < 0.001 at B4w, respectively, for VEGF). Multivariate analyses demonstrated that blood MUC1 and VEGF mRNA positivity at B0 and B4w were independent factors for predicting worse PFS and OS.ConclusionsMUC1 and VEGF mRNA positivity in blood seem to be indicators of unfavorable response and poor PFS and OS in patients with advanced NSCLC treated with gefitinib and may be promising noninvasive and repeatable markers for predicting efficacy of gefitinib treatment.
Highlights
Gefitinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, significantly improve prognosis in patients with advanced non-small cell lung cancer (NSCLC)
By using the highly sensitive real-time quantitative (RTQ)-Real-time quantitative-Polymerase chain reaction (PCR) assay in a representative series of NSCLC patients, we demonstrate that detections of MUC1 and vascular endothelial growth factor (VEGF) mRNA in peripheral blood are valuable diagnostic tools to identify a subset of NSCLC patients who benefit from gefitinib treatment
We showed that the positivity of VEGF mRNA in blood samples detected by the RTQPCR assay was correlated statistically with responsiveness to, and the progression-free survival (PFS) and overall survival (OS) of, gefitinib treatment
Summary
An EGFR-tyrosine kinase inhibitor, significantly improve prognosis in patients with advanced non-small cell lung cancer (NSCLC). On the basis of the data from clinical trials comparing EGFR-TKIs with placebo or chemotherapy, EGFR-activating mutation status appears to be the most valid marker for the selection of patients who would derive the most benefit from EGFR-TKI treatment [7,8,9,12,13,14]. Clinical studies have shown that even in patients with wild-type EGFR, EGFR-TKIs are either superior to placebo or not inferior to docetaxel chemotherapy as a second- or third-line therapy [9,10]. Practical clinical studies using blood markers that can predict treatment efficacy of NSCLC to EGFRTKIs are urgently required
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