Efficacy And Saffty Of Rh-endostatin Combined With Platinum-containing Regimen In The Treatment Of Advanced Triple Negative Breast Cancer

Objective:Evaluate the efficacy and safety of rh-endostatin combined with platinum-containing regimen in the treatment of advanced triple negative breast cancer.Methods:Retrospective analysis was performed on 21 cases of advanced triple negative breast cancer admitted to the Affiliated Cancer Hospital of Guangxi Medical University from January 2016 to May 2020.All patients were treated by rh-endostatin combined with platinum-containing regimen.Among them,the administration of rh-endostatin was 15mg/m~2/24h in 18 cases,which was continuous intravenously pumped from day 1 to day 7 for a cycle of 21 days.In 3cases,continuous venous pumping was not possible due to the refusal of deep venous catheterization,the administration of rh-endostatin was15mg/m~2/d,intravenous infusion for 6 to 8 hours,and the administration of rh-endostatin was intravenous infusion from day 1 to day 7 for a cycle of 21 days.Carboplatin:AUC=5,intravenous infusion on the 5th day,21days for a cycle,cisplatin:total amount of 75mg/m~2,intravenous infusion on the 5th to 7th day,21 days for a cycle,combined drugs include pemetrexed,docetaxel and gemcitabine.Efficacy was evaluated every 2cycles and adverse reactions were evaluated every cycle.Primary outcome measures were Objective response rate(ORR),Progression free survival(PFS).Secondary observation indicators included Disease control rate(DCR),Overall survival(OS),safety and tumor markers(CEA,CA125,CA153,CA199)before and after 2 cycles of treatment in the whole group.The rates were compared by Fisher exact probabilities.Kaplan-Meier estimates was used to draw survival curve and Log-rank test was used for survival analysis.Cox’s proportional hazard regression model was used for univariate analysis of possible prognostic factors.Wilcoxon rank sum test was used to compare the difference between non-normal pairs.P<0.05 was considered statistically significant.Results:1.All the patients were female,aged from 35 to 64 years old,with a median age of 47 years old.A total of 91 cycles of rh-endostatin combined with platinum-containing regimen were performed,and the median number of treatment cycles was 4(range:2～9).Efficacy was evaluated in all 21 patients,with 0 cases(0%)of complete remission,7cases(33.33%)of partial remission,10 cases(47.62%)of stable disease,and 4 cases(19.05%)of disease progression.The ORR and DCR of the whole group were 33.33%and 80.95%,respectively.Subgroup analysis,ORR of first-line treatment,second-line treatment and above treatment were 38.46%,25.00%,respectively,between the two groups there is no significant difference for ORR or DCR.In addition,according to age and menstrual status,ECOG score,number of organ metastases,with and without internal transfer,elevated or normal CA125 and CA153,there is no significant difference in each group of ORR and DCR.2.The median follow-up time was 11.07 months,and the 1-year survival rate was 55.6%.Eight patients(38.09%)were stable within 8months,and the longest was 14 months.The m PFS of the whole group were 5.49 months(95%CI,1.03～9.96),and m OS was 13.47 months(95%CI,12.03～14.91).The m PFS of first-line treatment,second-line treatment and above treatment were 8.21 months(95%CI,3.08～13.34)and 4.34 months(95%CI,2.85～5.83),respectively.The m OS of first-line treatment,second-line treatment and above treatment were 12.91 months(95%CI,7.89～17.93)and 19.32 months(95%CI,1.54～37.09),respectively.Univariate analysis of PFS and OS showed that age,menstrual status,ECOG score,number of treatment lines,number of organ metastases,presence or absence of visceral metastases,elevation of serum CA125 and serum CA153 were not correlated with PFS and OS(P>0.05).3.The whole group of 21 patients were all can assess the adverse reactions.theⅢ～Ⅳdegrees of hematology toxicity include anemia,leukopenia,thrombocytopeniareduceandgranulocytopenia reduce,incidence of anemia was 28.57%,incidence of leukopenia was19.05%,incidence of thrombocytopenia reduce was 14.29%,and incidence of granulocytopenia reduce was 9.52%.Non hematologic toxicity are mainlyⅠ～Ⅱdegrees,not seenⅢ～Ⅳdegrees.Eight patients(38.09%)presented abnormal electrocardiogram,presenting as sinus tachycardia and sinus arrhythmia,without chest distress,shortness of breath,palpitations or other discomfort.All kinds of adverse reactions were significantly improved after intervention,no drug-related bleeding,abnormal changes in blood pressure,significant decrease in left ventricular ejection fraction or death related to adverse reactions were observed in the whole group.4.Comparison of tumor markers before and after treatment:CEA,CA125,CA153 and CA199 levels before and after 2 cycles of treatment in the whole group,the group with CR+PR+SD and the first-line treatment group showed no significant difference(P>0.05).Conclusion:1.Rh-endostatin combined with platinum-containing regimen may have a good effect in the treatment of advanced triple negative breast cancer,and no significant increase in adverse reactions.2.The first-line treatment of rh-endostatin combined with platinum-containing regimen showed a tendency of prolonged PFS and further increased ORR compared with second-line and above treatment,suggesting that rh-endostatin combined with platinum-containing regimen may be more effective in the first-line treatment of advanced triple negative breast cancer.