Clinical Efficacy Of Apatinib In Second-line Treatment Failure Of Extensive Stage Small Cell Lung Cancer

Background and objectiveLung cancer has the most highly incidence and death rate in the world.Twenty to25%of all lung cancer are small cell type.It is a neuroendocrine tumor characterized by rapid proliferation and poor prognosis.In recent years,with the deepening comprehension of precision medicine,more targeted drugs have applied in clinic.Apatinib can inhibit tumor neovascularization by restraining the activity of tyrosine kinase and shows satisfactory anti-tumor effects and safety in various clinical trials.However,most studies of apatinib are focused on gastric cancer,there are few studies on lung cancer.The purpose of this study was to investigate the clinical efficacy and safety of apatinib in the treatment of extensive stage small cell lung cancer with second-line treatment failure,and to explore the influencing factors of prognosis.MethodsFrom August 2015 to February 2017,28 patients with extensive stage small cell lung cancer in Qianfoshan Hospital Affiliated to Shandong University who had a relapse or progression after second-line or above chemotherapy were enrolled.We divided the patients into apatinib treatment group(n=17)and support treatment group(n=11).In the apatinib treatment group,500mg daily was given with 28-days course until the disease progressed or an intolerable adverse reaction occurred.Patients experience grade 3 or 4toxicity should reduce the dose of apatinib to 250mg per day.If the patient still cannot tolerate the toxicity after dose reduction,treatment is recommended to be discontinued.In the other group,patients are given optimal support treatment.The clinical treatment effect of these two groups were compared and adverse reactions were observed.Statistical methods:SPSS22.0 software was used to analyze the data,Kaplan-Meier method was used for survival analysis,Log-Rank sequential test was used for screen out the factors affecting the prognosis,and Cox proportional hazard model for confirm the independent prognostic factors(P<0.05,there was statistically significant difference).Results1.Objective efficacy:A total of 28 patients were enrolled in this study.There were17 patients in the apatinib treatment group and 11 in the support treatment group.The overall response rate(ORR)accounts for 17.6%(3/17)in apatinib treatment group,and 0%in support group,the difference between the two groups was not statistically significant(P=0.258~*).Disease control rate(DCR)accounted for 76.5%(13/17)and 54.5%(6/11)respectively in the two groups which have no statistically significant difference(P=0.669~*).Serum tumor markers were monitored four weeks after apatinib treatment.CEA decreased from(23.14±12.69)ng/mL to(20.45±8.42)ng/mL;NSE decreased from(87.24±13.84)ng/mL to(45.93±11.07)ng/mL;ProGRP decreased from(2027.23±126.34)pg/mL to(1384.76±148.65)pg/mL.There was a statistically significant difference in NSE?ProGRP(P<0.05),however the decrease of CEA has no statistically significant(P>0.05).2.Survival status:The median progression free survival time(mPFS)of apatinib treatment group was 83 days while that of the support group was 49 days.There was a statistically significant difference in mPFS between the two groups(P<0.05).Median survival time(MST)for the two groups was 154 days and 101 days respectively,the difference was statistically significant(P<0.05).3.Adverse reactions:Adverse reactions were evaluated according to the National Cancer Institute General Toxicity Criteria(NCI-TCT v4.0).The results showed that grade3-4 adverse reaction of hypertension was three patients,bone marrow suppression,hand-foot syndrome,Oral mucositis,proteinuria was one patient respectively.Symptoms can be relieved after proper treatment or adjust the dose of apatinib.4.Univariate analysis:The ECOG score,degree of adverse reactions,and the number of tumor metastases were related to mPFS of the patients.The ECOG score,degree of adverse reactions was considered to be prognostic factors.Patients with ECOG score of0-1,adverse reactions of 1-2 have a superior prognosis.Gender,age was not related to prognosis.5.Multivariate analysis:The ECOG score(P=0.012)and the degree of adverse reactions(P=0.003)were confirmed to be independent prognostic factors for survival.Conclusion1.Apatinib have a certain curative effect on extensive stage small cell lung cancer with second-line treatment failure,the disease control rate is satisfied.2.Apatinib has acceptable side effects,mainly include hypertension,bone marrow suppression,hand-foot syndrome,oral mucositis,proteinuria,rash,diarrhea and transom-inase elevation.Most patients experienced grade 1-2 adverse reactions,fewer appear grade3-4 adverse reactions.Therefore,the medical compliance and tolerability are better,and it can improve the quality of life for patients to a certain extent.3.Log-Rank logistic analysis and Cox proportional hazards regression model showed that ECOG scores,and the degree of adverse reactions were independent prognostic factors of apatinib for extensive stage small cell lung cancer with second-line treatment failure.