Comparing Doublet And Single Cytotoxic Agent Chemotherapy As First-line Treatment In Elderly Patients With Advanced Non Small-cell Lung Cancer Efficacy And Safety Analysis

Background and Objective:Due to genetic testing technology and costs,the rate of genetic testing is low,about 40%.For elderly patients of lung cancer with unknown mutation status,chemotherapy is still occupy an important position.This article is to perform a clinical retrospective analysis and meta-analysis comparing doublet versus single agent chemotherapy in elderly patients with advanced non small-cell lung cancer efficacy and safety analysis(NSCLC).Methods:The first part:Collection patients from the First Affiliated Hospital of Dalian Medical University from January 2013 to December 2014,confirmed by cytology or histopathology of non-small cell lung cancer patients were aged ≥70 years,the median age was 74 years,stage Ⅳ,physical status score≤2 points,and who are expected to survive longer than three months and genetic testing is not carried out,and never receive targeted therapy or maintenance therapy.A total of 74 patients were analyzed,including doublet chemotherapy group of 43 patients,single-agent chemotherapy of 31 patients,retrospectively.The major endpoint was progression-free survival time(PFS),others were over all survival(OS),1-year survival rate(1-y SR),the overall objective response rate(ORR)and major grade 3/4 adverse events.All analyzes were performed using SPSS 17.0(tatistical package for the social science)for analysis,χ2 testing is used to identify the difference between the two groups.PFS,OS Survival Analysis use Kaplan-Meier method.P<0.05 was statistically significant.The second part:Collection of data from the following databases:China HowNet(CNKI),VIP database(VIP),Wanfang database,Chinese Biomedical Literature Database,PubMed et al.Selected 18 randomized controlled trials were analyzed by RevMan5.2 application software for data analysis,hazard ratio(HR)used to estimate the overall survival(OS),the relative risk(RR)is used to assess the objective response rate(ORR),1-year survival rate(1-SR)and grade 3/4 adverse events.Results:The first part:The doublet chemotherapy group has 43 cases,single-agent chemotherapy group has 31 cases.1.The combined chemotherapy group median PFS was 4.8±0.273 months,monotherapy group was 3.8±0.332 months,p=0.009;OS combined chemotherapy group was 12.1± 0.521 months,monotherapy group was 9.1±0.612 个 months,p=0.028;1-year survival rate,doublet chemotherapy group comparative monotherapy was 53.5%vs 22.6%,p=0.008,the differences were statistically significant.Regrouping deoenged on Whether received second-line or more chemotherapy,the result was in terms of doublet chemotherapy group or a single agent chemotherapy group who received second line chemotherapy or more had a better survival,p<0.05.2.The objective response rate(ORR)was 34.9%vs 12.9%,p=0.033;Disease control rate(DCR)was 76.7%vs 54.8%,p=0.047.3.Adverse events:The overall leucopenia and neutropenia occurred no significant difference between the two groups,p=0.10 and 0.169;overall thrombocytopenia doublet chemotherapy group contrast single-agent chemotherapy group HR 5.0,p=0.013;overall nausea and vomiting,HR 5.344,p=0.004;overall nephrotoxicity HR 9.091,P=0.017;3/4 grade of neutropenia,HR 2.21,p=0.013;3/4 grade neutropenia HR 3.616,p=0.033;Others were no statistical difference.The second part::18 studies(20 randomized trials:n=2451).1.Doublet chemotherapy group contrast single-agent chemotherapy group,OS(hazard ratio HR 0.78,95%CI 0.62,0.97 P=0.03 random effects model);1-year survival(RR 1.56,95%CI 1.14,2.12P<0.01).2.The objective response rate combined group comparative monotherapy group(RR 1.60,95%CI 1.40,1.83,P<0.01).3.The incidence of 3/4 grade of neutropenia double chemotherapy contrast monotherapy(RR 2.32,95%CI 1.03,5.21,P<0.05).The incidence of grade 3/4 neutropenia double chemotherapy contrast monotherapy(RR 1.44,95%CI 0.98,2.11,P<0.05).The incidence of grade 3/4 thrombocytopenia(RR 2.62,95%CI1.57,4.37,P<0.01).The incidence of 3/4 grade anemia(RR 2.29,95%CI 1.48,3.54,P<0.01).The incidence of grade 3/4 nausea and vomiting(RR 1.82,95%CI 1.16,2.86,P<0.05).Conclusions:1.Clinical retrospective data show that combined chemotherapy compared to single-agent chemotherapy prolonged PFS and OS significantly,improve 1-year survival,ORR and DCR,p<0.05.Patients receiving second-line chemotherapy had better PFS and OS,p<0.05.Doublet chemotherapy group had higher incidence of grade 3/4 myelosuppression,(leukopenia and neutropenia),overall thrombocytopenia and nephrotoxicity and nausea/vomiting.2.The meta-analysis of the two-drug combination compared to monotherapy significantly prolonged OS,improve 1-year survival rate and ORR,3/4 adverse event rates increased.