Efficacy And Safety Of EP Or IP Chemotherapy&Radiotherapy For Extensive-stage Small Cell Lung Cancer

Backgrounds:Lung cancer is a malignant tumor with high morbidity and mortality,and small cell lung cancer（SCLC）accounted for 10%-15%of the total incidence of lung cancer.The staging system of SCLC is generally adopted by the American veterans lung research group that is divided into local limited small cell lung cancer（LD-SCLC）and extensive stage small cell lung cancer(ED-SCLC.SCLC cells are characterized by short multiplication times and invasiveness,and about two-thirds of patients have developed into extensive stage by the time of diagnosis.SCLC is sensitive to chemotherapy and radiotherapy,and it is easy to develop secondary drug resistance in a short time,so the prognosis of newly diagnosed ED-SCLC patients is generally poor,the median progression-free survival（mPFS）is less than 6months,the middle overall survival（mOS）is less than one year,and the 2-year survival rate is less than 5%.According to the NCCN guidelines,etoposide plus platinum（EP）and irinotecan plus platinum（IP）are the standard first-line chemotherapy for SCLC.A recent meta-analysis suggested that IP regimen for chemotherapy of OS and 1-year survival was superior to EP regimen in the treatment of ED-SCLC,but the recent study from South Korea,North America and domestic multicenter randomizedⅢclinical trials showed that there was no obvious difference in the extensive stage small cell lung cancer treatment between EP solutions group and IP group.Therefore,it is still controversial whether the EP regimen or IP regimen is better or worse for chemotherapy,and the above studies did not consider the effect of chemotherapy combined with chest radiotherapy on the efficacy of SCLC.LD-SCLC chemotherapy combined with synchronous chest radiotherapy was recommended by the efficacy guidelines and widely used in clinical practice,but chest radiotherapy was not recommended for patients with LD-SCLC.The purpose of ED-SCLC radiotherapy is to improve local symptoms that is palliative treatment.A retrospective analysis in China suggested that chemotherapy combined with chest and cranial radiotherapy could improve PFS and OS in patients compared with chemotherapy combined with cranial radiotherapy,which may suggest that chemotherapy combined with chest radiotherapy can improve survival and prognosis in patients with ED-SCLC compared with chemotherapy alone.The current first-line chemotherapy regimen for ED-SCLC is controversial,we conducted a retrospective study on patients diagnosed with ED-SCLC in the third affiliated hospital of the Army Medical University.We compared the effects of EP and IP chemotherapy regimens on objective response rate（ORR）,disease control rate（DCR）,PFS and OS,and more than 3/4 grade toxic and side effects of different chemotherapy regimens were analyzed.Stratified analysis was performed to determine whether the patients received combined chest radiotherapy.We analyzed the influence of chest radiotherapy on patient survival,the influence of age,gender,smoking history,physical strength score and whether the total number of CD4+T cells and CD8+T cells in lymphocyte subsets is reduced on survival during chemotherapy,the proportion and efficacy of second-line chemotherapy.The Research Object The selected objects were patients with SCLC who underwent pathological diagnosis and treatment in the third affiliated hospital of the Army Medical University（Institute of Field Surgery）from September 1,2013 to September 1,2017.According to the inclusion and exclusion criteria,149 patients with ED-SCLC were screened,including 125 males and19 females.The Research Methods General information including age,gender,smoking history,previous medical history,course of disease,PS score,height and weight.Patients’chemotherapy regimens,number of chemotherapy cycles,whether they received chest radiotherapy or not,toxic and side effects,and efficacy of chemotherapy,total number of CD4+T cells and CD8+T cells in PFS,OS,lymphocyte subsets were collected.According to the first-line chemotherapy,the patients were divided into EP chemotherapy group and IP chemotherapy group.Primary observation and treatment including PFS,OS,grade 3/4 and above toxic and side effects.Secondary observation indicators including DCR,ORR,total number of chemotherapy and proportion and efficacy of second-line chemotherapy.We did stratified analysis of whether the patients received chest radiotherapy or not.In addition,the influence of the total number of CD4+T cells and CD8+T cells in lymphocyte subsets on survival was analyzed.We used SPSS 22.0 statistical software for data analysis,kaplan-meier method for survival analysis,and log-rank test for survival comparison between groups.Survival prognostic factors were analyzed by Cox regression model.p<0.05 was considered statistically significant.Results 1.Among 144 patients with ED-SCLC,65 patients received first-line EP chemotherapy and 79 patients received first-line IP chemotherapy,a total number of 52patients received chest radiotherapy,and 46 patients had a low total number of CD4+T cells or CD8+T cells in the lymphocyte subsets.2.The ORR ratio of EP group was 67.6%,and that of IP group was 57.0%,p=0.243.The ORR ratio of EP group was slightly better than that of IP group,but there was not statistically significant difference between the two groups.DCR was 93.8%in EP group and 92.4%in IP group,p=0.328.DCR was slightly better in EP group than IP group,but there was not statistically significant difference between the two groups.3.mPFS was 5.05months in EP group and 4.30 months in IP group,p=0.65.mPFS in EP group was slightly longer than that in IP group,but there was not statistically significant difference between the two groups.mOS in EP group was 13.95 months,and mOS in IP group was 14.10months,p=0.120.mPFS in IP group was slightly longer than that in EP group,but there was not statistically significant difference between the two groups.4.mPFS was 5.4 months in the chemotherapy combined with chest radiotherapy group,and 3.8 months in the non-radiotherapy group,p=0.016.There was statistically significant difference between the two groups.5.The average total cycles of chemotherapy were 5.8 times in EP group and 5.22 times in IP group,p=0.250.The total cycles of chemotherapy were more in EP group than IP group,but there was not statistically significant difference between the two groups.6.Among the 144 patients,55 patients received second-line or above chemotherapy,and the proportion was 38.19%.The ORR₂ of the EP regimen group was 21.4%,and that of the IP group was 29.6%in the second-line chemotherapy.The efficacy of the IP group was slightly higher than that of the EP group when receiving the second-line treatment,but the difference was not statistically significant（p=0.231）.7.mPFS of the normal lymphocyte subgroup group was 5.0 months,mPFS of the low lymphocyte subgroup group was 3.4 months,mPFS of the normal lymphocyte subgroup group was longer than that of the low lymphocyte subgroup group,and there was statistically significant difference between the two groups.（p=0.011）.mOS of the normal lymphocyte subgroup was 15.2 months,and that of the low lymphocyte subgroup was 9.0 months.mOS of the normal lymphocyte subgroup was longer than that of the low lymphocyte subgroup,and the difference was statistically significant（χ²=11.351,p=0.001）.8.We found that the lymphocyte subgroup,chest radiotherapy and age are the influence factors of patients with OS,but age,gender,smoking history,PS score,first-line chemotherapy are not the influence factors of PFS through to the patients’age,gender,smoking history,PS score,first-line chemotherapy regimens,lymphocyte subgroup and whether combined with chest radiotherapy or not.We found that lymphocyte subsets（p=0.039）and whether combined with chest radiotherapy or not（P=0.046）were independent influencing factors of OS in patients with extensive SCLC,while age was not an independent influencing factor of SCLC（p=0.182）when age,lymphocyte subsets,and whether combined with chest radiotherapy or not were included in COX multivariate analysis.9.5 cases（7.7%）had diarrhea,34 cases（52.3%）had neutropenia,and 48 cases（73.8%）had anemia in EP group,while diarrhea occurred in 37 patients（46.8%）,neutropenia occurred in 18 patients（22.8%）,and anemia occurred in 32 patients（40.5%）in IP group.The incidence of diarrhea in IP group was higher than that in EP group,and neutropenia and anemia in EP group were higher than that in IP group,and there was statistically significant difference between the two groups.（p=0.020,0.001,0.013）.Conclusion For patients with ED-SCLC,there was no significant difference in the efficacy of EP regimen and IP regimen in chemotherapy,and the combination of chest radiotherapy could significantly improve the prognosis of patients.Patients with normal T4 and T8 in the lymphocyte subgroup had a better prognosis than those with low T4 and T8.Neutropenia and anemia were higher in the EP group,and diarrhea was higher in the IP group.Lymphocyte subsets and whether combined with chest radiotherapy（p=0.046）were independent factors affecting OS in patients with extensive SCLC.