The Detecting Of Epidermal Growth Factor Receptor Gene Mutations And Observing The Efficacy Of Chemotherapy Of Advanced Lung Adenocarcinoma Patients

[Background]:Lung cancer is a serious threat to human health,and new cases per year in global are about1.5million.If smoking and air pollution in our country can not be controlled, to2025, the number of new lung cancer patients per year in our country will be over one million and our country will have the most lung cancer patients in the world. One research report from the China Disease Control Centre shows, the rate of lung cancer occurring and death goes up obviously in recent years, and it shows a trend to the younger generation, the result of clinical treatment is also poor. In the past30years, the rate of cancer occurring has risen obviously in China, the rate of lung cancer which ranked the fourth in1970s has jumped to the first in2000. From1970s till now,the rate of lung cancer shows a trend to keeping rising continuously,as is similar to the whole world, the rate of lung cancer occurring and death among male is higher than the rate among female. While in China it varies in different area,the rate in the cities is much higher than the rate in the countryside. The age of lung cancer occurring and death goes up quickly after40, and it comes to the peak at70. The report also shows the trend of lung cancer to the young people. It is said from the report the lunge cancer does not show much in the early stage, the patients who come for treatment have come to the late stage, that is why the result is quite poor. So the crux of improving the treatment of lung cancer is to diagnose it as early as possible.earlier. In the resent20years, due to the development of photo diagnosis and clinical treatment technology,the surviving rate among lung cancer patient who have been accepted by the hospital has goes up to25%to30%in five years, the five years surviving rate of lung cancer is15%in the developed compared to the below10%in China. Most of the patient who come for treatment have come to the latest age,and the opportunity of taking an operation has gone.Non-small cell lung cancer (accounting for85%of the total number of lung cancer) is the most common type of lung cancer, and also is the most important reason which threaten the survival of patients with lung cancer.according to lung cancer TNM new staging system proposed by International Association,lung cancer is divided to0-IV period.0is Carcinoma in situ,and IV has distant metastasis.20%of all are IA, ⅠB, ⅡA and ⅡB NSCLC patients,in which surgical treatment can be used,50%to80%of which receive a5-year survival;about40%of all patients are ⅢA and ⅢB, ⅢA patients can be treated by surgery,and the5-year survival is just only10%to30%;IIIB patients have no surgical treatment can be used.IV patients are not fit for surgery,because thy have distant metastasis,and the majority of metastases are in the liver,bone,adrenal gland,brain,and bilateral lungs.So,Ⅰ-ⅢA patients can consider surgery,but ⅢB and Ⅳ patients are not suitable for surgical treatment.After surgery,I-IIIA patients also need chemotherapy,except IA and some IB patients.IIIB and IV patients can only choose to traditional chemotherapy or local radiotherapy.the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) is with platinum drugs and the third generation of new drugs (paclitaxel, gemcitabine, vinorelbine Bin),and the total effective rate was30%-40%,the overall survival time was10months,1year survival rate was40%. After first-line treatment, the vast majority of patients will progress and commonly use second-line chemotherapy drugs such as docetaxel,pemetrexed,but efficiency does not exceed10%.In recent years, several large clinical trials show the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor for second-line treatment is not worse than chemotherapy,and has less Side effect.Biological targeted therapy is a hot study of non-small cell lung cancer. Targeted therapy which have a higher selectivity, less toxicity is a new trend for cancer treatment in future.common therapeutic targets of molecular targeted therapy in Lung cancer have:cell receptors,signal transduction and anti angiogenesis.But the epidermal growth factor receptor (EGFR) is the most important target.Lynch and Paze,first reported that in non-small cell lung cancer,the mutations of tyrosine kinase coding region in epidermal growth factor receptor is a necessary prerequisite for targeted drugs works.The results show that EGFR tyrosine kinase inhibitor gefitinib(Gefitinib; trade name:Iressa) is effective on80%of the mutant tumor,but ineffective on non-mutant wild-type tumors,which was confirmed by many scholars from various countries.The optimum patients can be filtered out from advanced lung cancer patients by EGFR gene detection, and targeted therapy to improve drug efficacy significantly.Studies of some scholars in globe show that in non-small cell lung cancer, adenocarcinoma has a high mutation rate, nearly50%,of which bronchioloalveolar carcinoma has a higher mutation rate;there is also a higher mutation rate in women than men,in no smoking than smoking patients; while the mutation rate of squamous cell carcinoma is very low, about5%to10%, so targeted drugs were mainly used in advanced lung adenocarcinoma patients with EGFR gene mutations. Advanced lung adenocarcinoma patients with EGFR mutation receiving chemotherapy and targeted drugs have a better efficacy than receiving chemotherapy alone.However, due to economic and other constraints, most of the advanced lung adenocarcinoma patients with EGFR gene mutations are unable to accept the targeted therapy, only receiving chemotherapy.So,are there differences between advanced lung adenocarcinoma patients with EGFR gene mutations receiving chemotherapy alone or chemotherapy and targeted drugs and patients with Wild-type EGFR receiving chemotherapy?Some studies in abroad report:EGFR gene mutations may increase the efficacy of platinum drugs.[Objective]:Observing the overall EGFR gene mutation rate of advanced lung adenocarcinoma patients, the influence of Gender and smoking to EGFR gene mutation rate; Observing the progression-free survival and overall survival between advanced lung adenocarcinoma patients with EGFR gene mutations receiving chemotherapy alone or chemotherapy and targeted drugs and patients with no EGFR gene mutations receiving chemotherapy.[Method]:From October2010to May2011, we collected31locally advanced or metastatic lung adenocarcinoma patients who were confirmed by pathology or cytology, and all were IIIB or IV according to lung cancer TNM new staging system proposed by International Association.Detect EGFR gene with DNA Sequencing in all advanced lung adenocarcinoma patients.Patients with Wild-type EGFR gene were treated with four cycles chemotherapy which contained Platinum, once every three week.Patients with EGFR gene mutations were treated with four cycles chemotherapy which contained Platinum, once every three week,after chemotherapy all patients with EGFR gene mutations were observed or given Iressa maintenance therapy, oral treatment of250mg/d until disease progression or occurrence of intolerable side effects according to the actual situation.Before chemotherapy all patients were given chest X-rays or chest enhanced CT every time,and after chemotherapy all patients were given chest X-rays or chest enhanced CT every two months,also we gave PET-CT or head-enhanced MR+breast enhancement CT+whole body bone scan+ abdominal B ultrasound to observe the disease progression. Collect the clinical and pathological data of all patients and follow up in twelve months with telephone or Communication.When the overall survival time of patients was less than twelve months,we followed up until they died.[Results]:There were15patients with EGFR gene mutations in all advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was48.4%;There were8patients with EGFR gene mutations in23male advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was34.8%;There were7patients with EGFR gene mutations in8female advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was87.5%;There were6patients with EGFR gene mutations in18smoking advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was33.3%;There were9patients with EGFR gene mutations in13non-smoking advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was69.2%;There were7patients with EGFR gene mutations in8non-smoking female advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was87.5%;There were2patients with EGFR gene mutations in5non-smoking male advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was40.0%;There were6patients with EGFR gene mutations in18smoking male advanced lung adenocarcinoma patients,the rate of EGFR gene mutation was33.3%;There were2patients lost to followed up in all advanced lung adenocarcinoma patients,the rate of following up was93.5%.15advanced lung adenocarcinoma patients with Wild-type EGFR gene were given chemotherapy containing Platinum,and the progression-free survival period was from2to12months,progression-free survival was(4.5±2.9)months, the overall survival period from3to12months, overall survival period was(8.8±3.8)months;7advanced lung adenocarcinoma patients with EGFR gene mutations were given chemotherapy containing Platinum,and the progression-free survival period was from3to12months,progression-free survival was(7.1±3.7)months, the overall survival period from5to12months, overall survival period was(10.3±2.6)months;7advanced lung adenocarcinoma patients with EGFR gene mutations were given chemotherapy and Iressa maintenance treatment,and the progression-free survival period was from1to12months,progression-free survival was(8.4±5.0)months, the overall survival period was all more than12months, overall survival period was(12.0±0.0)months.comparing the PFS and OS in each other,there was significant difference between advanced lung adenocarcinoma patients with Wild-type EGFR gene given chemotherapy and advanced lung adenocarcinoma patients with EGFR gene mutations given chemotherapy and Iressa(P<0.05),and there was no significant difference between others(P>0.05).[Conclusion]:The rate of EGFR gene mutation in advanced lung adenocarcinoma patients is close to50%, which is similar to the reported.there is a higher EGFR gene mutation rate in women than men,in no smoking than smoking patients,and the rate of EGFR gene mutation is highest in female non-smoking advanced lung adenocarcinoma patients.Advanced lung adenocarcinoma patients with EGFR mutation receiving chemotherapy and targeted drugs have a better efficacy than receiving chemotherapy alone,and advanced lung adenocarcinoma patients with EGFR mutation receiving chemotherapy alone also have a better efficacy than advanced lung adenocarcinoma patients with Wild-type EGFR gene receiving chemotherapy.