Clinical Research Of Appatinib In Advanced Soft Tissue Sarcoma With Failure Of First-line Chemotherapy

Background and objectiveSoft tissue sarcoma（SSS）is a kind of malignant tumors originating from mesen-chymal tissue.Most of them occur in extremities,trunk and retroperitoneum,accounting for about 1%of adult malignant tumors and 15%of children malignant tumors.WHO classified STS into more than 50 subtypes,including liposarcoma,angiosarcoma,leio-myosarcoma,fibrosarcoma,synovial sarcoma,pleomorphic undifferentiated sarcoma and malignant schwannoma.STS generally has the characteristics of high malignancy and short median survival.After traditional surgical treatment,50%of patients will have recurrence or metastasis.However,advanced STS is less sensitive to radiotherapy and chemotherapy and has poor therapeutic effect.In recent years,with the deepening of cancer signaling pathway research,targeted drugs in some cancer therapies have achieved positive results,as well as the continuous exploration of new treatment methods,the treatment of this kind of disease has ushered in the dawn^[43].However,only Pazopanib has been approved by the Food and Drug Administration for second-line treatment of advanced STS.However,although Pazopani has been listed in China for more than one year,the price is still high,and ordinary families can not afford it.Therefore,for advanced STS patients in China,finding a drug with similar effect and moderate price is an important way to successfully overcome the waiting period.Apatinib is a self-developed inhibitor targe-ting small molecules of vascular endothelial growth factor tyrosine kinase,which combines with vascular endothelial growth factor receptor 2 to block angiogenesis and inhibit the growth of tumors^[12].Studies have shown that apatinib is effective in some subtypes of advanced STS.In this study,a retrospective control study was conducted to analyze the clinical efficacy and safety of apatinib in the treatment of advanced STS with failure or intolerance to chemotherapy,and to further explore the related factors affecting the pro-gnosis of treatment.MethodsThirty patients with advanced STS who failed or did not tolerate chemotherapy were retrospectively collected from Qianfoshan Hospital of Shandong Province from August2016 to May 2018.They were divided into two groups:the single-drug treatment group（20 cases）and the supportive treatment group（10 cases）.Therapeutic regimen:The treatment group was given apatinib 500 mg/d orally for 28 days as a course of treatment until the disease progressed or intolerable adverse reactions occurred.For patients with grade 3 or 4 toxicity,the dose of Apatinib was reduced to 250 mg per day.If the patient still showed intolerable toxicity after the dose was lowered,the treatment should be discontinued.The control group was given the best supportive treatment,including nutria-tional support,pain relief,infection prevention,immunity improvement and symptomatic treatment.To observe the clinical effect of the two groups,and to evaluate the occurrence and tolerance of the adverse reactions of apatinib.Statistical methods:SPSS23.0 software was used for data analysis,Maple 2 test was used for comparison of short-term curative effect,t test was used for counting data;Kaplan-Meier method was used for survival analysis and Log-Rank time series test was used to screen out possible factors affecting prognosis,and Cox regression model was established to analyze multiple factors to confirm independent factors affecting survival.P<0.05 thought the difference had statistical significance.Results1.Objective efficacy analysis:30 patients in the treatment group were evaluated systematically.There was no CR in the treatment group and the control group.Among them,there were 2 cases of PR,14 cases of SD,4 cases of PD,4 cases of SD and 6 cases of PD in the treatment group and the control group.The ORR of the two groups were 10%and 0%（P=0.540）,respectively,with no significant difference（P>0.05）;DCR was 80%and 40%（P=0.4）,respectively.The difference was statistically significant（P<0.05）.2.Survival:The progression-free survival（m PFS）was 4.7 months（95%Cl:3.1-6.5months）,2.9 months（95%Cl:1.5-4.4 months）,P=0.02（P<0.05）,the median survival（MST）was 9.5 months（95%Cl:8.5-12.4 months）,7 months（95%Cl:4.0-10.1 months）,P=0.016（P<0.05）.3.Adverse reactions:Adverse reactions were evaluated according to NCT-TCT4.0.The results showed that the main adverse reactions in patients treated with apatinib were grade 1-2.Among the patients with grade 3-4 adverse reactions,1 case had grade 3 hand-foot syndrome and mucositis,1 case had grade 3 gastrointestinal reactions,and one case had proteinuria adverse reactions..The adverse reactions were alleviated by reduction or symptomatic treatment.4.Univariate analysis:Log-rank time series was used to examine the therapeutic efficacy of 20 patients in the treatment group.The results showed that the primary site（P=0.039）and the number of metastases（P=0.02）were correlated with the overall survival time of patients（P<0.05）,while gender,age,ECOG score,operation,number of treatment lines,tolerable dose,and whether combined therapy were not related to the prognosis of patients.（P>0.05）5.Multivariate analysis results:The related factors obtained by single factor were brought into COX proportional risk regression model,and related multifactor analysis was carried out to screen out independent influencing factors.The results showed that the treat-ment regimen（P=0.023）and the number of metastases（P=0.027）were correlated with the overall survival time of patients（P<0.05）.The prognosis of patients with metastases less than 2 treated with Apatinib was better.