The Impact of Smoking Status on the Efficacy of Erlotinib in Patients with Advanced Non-small Cell Lung Cancer

Background and objective Erlotinib is a targeted treatment for advanced non-small cell lung cancer. Smoking status may be one of influencing factors of the efficacy of erlotinib. The aim of this study is to explore the impact of smoking status on the efficacy of erlotinib in patients with advanced non-small cell lung cancer. Methods Patients with nonsmall cell lung cancer who had been previously treated with at least one course of platinum based chemotherapy received 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression-free survival, overall survival were analyzed in the different smoking status groups. Kaplan-Meier method was used to analyze the survival rate. Results Fortyeight patients were enrolled into the study from December 2005 to September 2006. We followed up these patients until 28th December, 2008. Median follow up time was 30 months. The compliance rate was 100%. The response rate was 32.1% in the smoking group and 35% in the never smoking group (P=0.836); The median progression-free survival was 3 months and 9 months, respectively (P=0.033). The median overall survival was 5 months and 17 months, respectively (P=0.162). Conclusion Erlotinib is an effective drug for advanced non-small cell lung cancer patients with different smoking status. Progressionfree survival is better in the never smoking patients than the smoking patients

Analysis of Differentially Expressed Proteins in Self-Paired Sera of Advanced Non-small Cell Lung Cancer Patients Responsive to Gefin

Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy in advanced non-small cell lung cancer. Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR) after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. All samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1) was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z), 3242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04) were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73) up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation

Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression

<p>Abstract</p> <p>Background</p> <p>The anaplastic lymphoma kinase (<it>ALK</it>) gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of <it>ALK </it>include <it>NPM</it>, <it>EML4</it>, <it>TPM3</it>, <it>ATIC</it>, <it>TFG</it>, <it>CARS</it>, and <it>CLTC</it>. Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer.</p> <p>Results</p> <p>RACE-coupled PCR sequencing was used to assess <it>ALK </it>fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC) patients. Within this cohort, the <it>EML4</it>-<it>ALK </it>fusion gene was identified in 12 tumors (11.6%). Further analysis revealed that <it>EML4</it>-<it>ALK </it>was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking <it>EGFR </it>and <it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion was associated with non-smokers (<it>P </it>= 0.03), younger age of onset (<it>P </it>= 0.03), and adenocarcinomas without <it>EGFR</it>/<it>KRAS </it>mutations (<it>P </it>= 0.04). A trend towards improved survival was observed for patients with the <it>EML4</it>-<it>ALK </it>fusion, although it was not statistically significant (<it>P </it>= 0.20). Concurrent deletion in <it>EGFR </it>exon 19 and fusion of <it>EML4</it>-<it>ALK </it>was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the <it>EML</it>-<it>ALK </it>fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; <it>P </it>= 0.0018). However, expression of EML4 did not differ between the groups.</p> <p>Conclusions</p> <p>The <it>EML4</it>-<it>ALK </it>fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking <it>EGFR</it>/<it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of <it>EML4</it>-<it>ALK</it>-positive patients.</p