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Background and purpose:New treatment methods should be explored for non-small cell lung cancer (NSCLC) patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). This study compared the curative effect of pemetrexed with geiftinib or pemetrexed alone in advanced NSCLC with acquired resistance to EGFR-TKI.Methods:This study included 62 NSCLC patients with advanced EGFRgene mutation and acquired resistance to EGFR-TKI. Among those, 32 patients were treated with pemetrexed and geiftinib, and 30 patients treated with geiftinib alone. The differences in outcomes between the two strategies were assessed.Results:Objective response rate (ORR) was 46.9% for those treated with pemetrexed and geiftinib and 20%for those treated with pemetrexed alone(χ2=4.933,P0.05). The median progression-free survival (PFS) was 8.0 months on pemetrexed and gefitinib group and 6.3 months on pemetrexed alone (χ2=8.063,P0.05). Higher occurrence of leukocytopenia and rash was observed in the pemetrexed and geiftinib group than in the pemetrexed group (P0.05).Conclusion:This study was to demonstrate that continuation of EGFR-TKI with pemetrexed in patients with acquired resistance improves outcomes compared with pemetrexed alone. An improved response rate and PFS were observed in this study. A larger prospective clinical trial is needed to further evaluate this promising strategy.
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Background and purpose:Non-small cell lung cancer (NSCLC) patients who have good curative effect on epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) will inevitably acquired drug resistance. It will effect the survival directly. In contrast, few studies have found that EGFR-TKI effectively acquired drug resistance in patients with clinical characteristics. We investigated clinical characteristics of NSCLC patients who experienced acquired drug resistance during geiftinib therapy. Methods:To review the treatment from the beneift of patients with non-small cell lung cancer. All of the data were obtained from Jan. 2007 to Jan. 2014 in Xinjiang tumor hospital. The treatment for failure of acquired drug resistance of clinical manifestations, time to progress (TTP) and post-progression survival (PPS) were retrospectively analyzed. Results:The total collection of 417 patients. Median TTP was 10.2 months (95%CI:9.5-10.9). The TTP of women adenocarcinoma patients who didn’t smoke signiifcantly extended. When acquired drug resistance happened, 63.3%of patients appeared worse symptoms. The progress of the disease is as follows:209 cases (58.4%) from the primary lesion, 137 cases (38.3%) before the transfer, 194 cases (54.2%) of new happened. Patients of epidermal growth factor receptor (EGFR) wild type had more tendencies of symptomatic deterioration and new central nervous system (CNS) transfer than patients of EGFR mutation type. Patients of exon 19 deletion and L858R mutations on the new transfer were different (41.4%vs 6.3%, P=0.02). PPS was 8.9 months (95%CI:7.4-10.4). Smoking history, performance status (PS) score, new CNS lesions and the subsequent chemotherapy is independent factors of PPS. Conclusion:This study suggests that the clinical manifestations of acquired drug resistance according to EGFR mutation status and EGFR mutation genotype may be different. In addition, after the treatment of acquired drug resistance in patients with non-small cell lung cancer, the subsequent clinical beneift from chemotherapy are also associated with PPS.
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Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.
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Background and purpose:Hepatocyte growth factor (HGF) induce epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in non-small cell lung cancer (NSCLC) cells, the mechanism might be related with activation of c-Met. The present study aimed to explore whether c-Met inhibitor SU11274 reverse gefitinib resistance induced by HGF in differentEGFR gene types of NSCLC.Methods:PC9 (EGFR-activating mutant), H292 (EGFR-wild type) and A549 (EGFR-wiled) were chosen. The experiments were divided into 6 groups:C group (control), H group (HGF), G group (geiftinib), S group (SU11274), GH group (geiftinib+HGF), GSH group (geiftinib+SU11274+HGF). The cell survival was measured by MTT assay; the cell apoptosis was measured by lfow cytometry (FCM); the expressions of c-Met, Stat3, Akt and Erk1/2 protein were examined by Western blot.Results:Gefitinib inhibited cell growth of 3 cells lines in a dose-dependent manner, and treating with HGF could relieve inhibition of cell growth caused by geiftinib. The cell survival when treating the HGF-induced cell lines with defferent concentration of geiftinib combined with SU11274 was signiifcantly decreased than that when treating HGF-induced cell lines with geiftinib alone. In 3 cell lines, the apoptosis rate in HGS group was higher than that in HG group (P<0.05). In three cells lines, the p-Met, p-Stat3, p-Akt and p-Erk1/2 expressions in HGS group were lower than that in HG group (P<0.05).Conclusion:SU11274 reversed geiftinib resistance induced by HGF in different EGFR gene types of NSCLC cells, the mechanism might be related with inhibiting the HGF-induced activation of c-Met and its downstream signaling pathway.