Serum CEA Level Is Associated With Efficacy And Prognosis Of EGFR-TKI Treatment In Non-small Cell Lung Cancer

Background and purposeNon-small cell lung cancer (NSCLC) is the most common cause of cancer-related mortality worldwide, accounting for more than one million deaths annually. The cytotoxic chemotherapy can potentially prolong survival of patients with advanced cancer, one-year survival rate is almost doubled for patients with advanced NSCLC who received standard platinum-based chemotherapy;but the benefit of maintenance is not consistent chemotherapy has only shown an improvement in overall survival of 2-4 months. The cytotoxic chemotherapy has reached a therapeutic plateau.Based on these results, EGFR-TKI has been approved for treating patients with NSCLC upon the failure of other chemotherapies. Two inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK), erlotinib and gefitinib, have been shown to possess clinical efficacy for advanced NSCLC. EGFR is a transmembrane protein that induces a signal transduction cascade upon ligand binding. It is activated through autophosphorylation of a tyrosine residue in the cytoplasmic domain, causing the receptor to dimerize and internalize, and triggering a cascade leading to cellular proliferation, inhibition of apoptosis, and other cancer-related activities. EGFR-TKI inhibit this cascade by blocking autophosphorylation.But,in rencent years,the response rate to EGFR-TKI used as the second line treatment is less than 10% in the unseleted advanced NSCLC.For example,the response rate of erlotinib is 8.9% in BR.21 and the response rate of gefitinib is 9.7% in INTEREST. The response rate of EGFR-TKI as maintenance treatment or adjuvant therapy is inferior to placebo in unseleted NSCLC in BR.19 and SWOGS0023. Patients'characteristics, such as adenocarcinoma histology, female sex, non-smoking history, and Asian race, are associated with an increased response to EGFR-TKI.The objective response rate of EGFR-TKI is 43% in IPASS.The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer.The response rate of mutation carriers is roughly 70-80%. In addition, the method is still not generally established in practice.The detection of mutations in EGFR is high qualified and costly in tissue selection of human tumor, instrument and quality control. It is worth mentioning that, EGFR mutations in the same tumor, the primary tumor and metastases may be heterogeneous. A higher proportion of the EGFR mutation in same tumor tissues has a better efficacy to EGFR-TKI therapy; the EGFR mutation status is not the same both in primary and metastatic tumors. These factors also resulted the indifferences in the efficacy of EGFR-TKI. It is not the only indicator to judge the EGFR-TKI efficacy to detect EGFR mutation in primary tumors. Varieties of limits to detect EGFR mutation, the search for a new biomarker as an aid in EGFR mutation detection is very valuable. This study investigated the relationship between the serum CEA level and the therapeutic effect in advanced NSCLC treated with EGFR-TKI,and analysed if Serum CEA level can be regard as predictive factor for therapeutic effect and prognosis.MethodsWe retrospectively reviewed 88 NSCLC patients, including 69 adenocarcinoma and 19 non-adenocarcinoma who admitted in our hospitals from July 2007 to Noverber 2010.All patients received one or more regimens of chemotherapy before receiving EGFR-TKI treatment. The serum levels of CEA was determined with Electrochemiluminescence immunoassay (ECLIA) within four weeks before starting the EGFR-TKI treatment. According to the manufacturer, the normal range of serum CEA level is below 5.0ng/ml. The clinical responses to the drug were defined according to the response evaluation criteria of RECIST for patients with measurable disease.The statistical test between the serum CEA level and the therapeutic effect were performed by SPSS17.0. Statistical significance for the various clinicopathological factors among compared categories was evaluated using the Mann-Whitney test. A survival analysis for each categorical variable regarding progression-free survival and overall survival was estimated according to the Kaplan-Meier method. The statistical significance of the differences between the survival curves was evaluated by the log-rank test. A univariate analysis of several prognostic factors was carried out using the Cox proportional hazards model. Statistical difference was considered to be significant if the P value was below 0.05.Results1.In the cases whose serum CEA level was lesser than 5 ng/ml, the effect rate (including complete remission and partial remission, CR+PR) was 18.2%(6/33), the stable disease (SD) rate was 18.2%(6/33) and the progressive disease (PD) rate was 63.6%(21/33). But in the cases whose serum CEA level was equal or higher than 5 ng/ml, the effect rate (CR+PR) was 30.9%(17/55), the SD rate was 43.6%(24/55) and the PD rate was 25.5%(14/55). The two EGFR-TKI treatment response rates had greatly statistical difference (P=0.003). The patients who had a higher serum CEA level had a better therapeutic outcome, while for those with a low CEA level, a poor therapeutic effect was observed.2.Survival analysis suggested that high serum CEA level was associated with long progress free survival (PFS) and good prognosis (P=0.020, P=0.019).ConclusionSerum CEA level can be regard as predictive factor for therapeutic effect and prognosis in advanced NSCLC treated with EGFR-TKI.