Abstract
BackgroundIn order to improve the outcome of patients with non-small cell lung cancer (NSCLC), a biomarker that can predict the efficacy of chemotherapy is needed. The aim of this study was to assess the role of EGFR mutations and ERCC1 in predicting the efficacy of platinum-based chemotherapy and the outcome of patients with NSCLC.MethodsWe conducted a retrospective study to analyze the relationships between EGFR mutations or ERCC1 expression and progression-free survival (PFS) in patients with NSCLC who received platinum-based chemotherapy. EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and immunohistochemistry was used to examine the expression of ERCC1 in tumor samples obtained from the patients.ResultsAmong the NSCLC patients who received platinum-based chemotherapy, the median PFS was significantly better in those who had never smoked and those with exon 19 deletion, and the median overall survival (OS) was significantly better in those who had never smoked, those with exon 19 deletion, and women. Cox regression analysis revealed that exon 19 deletion and having never smoked were significantly associated with both PFS and OS. Subset analysis revealed a significant correlation between ERCC1 expression and EGFR mutation, and ERCC1-negative patients with exon 19 deletion had a longer PFS than the other patients; ERCC1-positive patients without exon 19 deletion had a shorter PFS than the other patients.ConclusionsOur results indicate that among NSCLC patients receiving platinum-based chemotherapy, those with exon 19 deletion have a longer PFS and OS. Our findings suggest that platinum-based chemotherapy is more effective against ERCC1-negative and exon 19-positive NSCLC.
Highlights
Lung cancer is the leading cause of cancer death worldwide [1]
Somatic activating mutations of the epidermal growth factor receptor (EGFR) gene have been identified as a major determinant of the clinical response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib in patients with non-small cell lung cancer (NSCLC)
The chemotherapy regimens consisted of carboplatin-paclitaxel in 55 patients, carboplatin-gemcitabine in 12, carboplatin-pemetrexed in 4, carboplatin-vinorelbine in 1, cisplatin-vinorelbine in 18, cisplatin-docetaxel in 4, cisplatin-gemcitabine in 4, cisplatin-vinorelbinegemcitabine in 3, cisplatin-pemetrexed in 1, and cisplatinetoposide in 1
Summary
Lung cancer is the leading cause of cancer death worldwide [1]. The epidermal growth factor receptor (EGFR) is considered to be an important molecular target in lung cancer therapy. Somatic activating mutations of the EGFR gene have been identified as a major determinant of the clinical response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib in patients with NSCLC. Most of these mutations occur in exons 19 to 21, which encode the tyrosine kinase domain of the receptor, the most common being deletions in exon 19 (such as delE746-A750) and the L858R point mutation in exon 21. The aim of this study was to assess the role of EGFR mutations and ERCC1 in predicting the efficacy of platinum-based chemotherapy and the outcome of patients with NSCLC
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