Efficacy And Safety Analysis Of Recombinant Human Endostatin(Endostar) Combined With Chemoradiotherapy For Locally Advanced Cervical Cancer

Background:Recombinant human endostatin(Endostar)is a multi-target endogenous angiogenesis inhibitor,which can inhibit tumor angiogenesis by blocking the proliferation and migration of vascular endothelial cells and inducing endothelial cell apoptosis,thus inhibiting tumor growth,metastasis and invasion.Compared with bevacizumab,an anti-angiogenic drug commonly used in clinic,Endostar has the advantages of low bleeding risk,low toxicity and side effects,and is not easy to drug resistance.Although there are more and more reports about the treatment of cervical cancer with Endostar combined with radiotherapy and chemotherapy,the efficacy and safety of this treatment strategy are still controversial.This study intends to review and analyze the efficacy,safety and prognostic factors of Endostar combined with radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer,so as to provide important reference value for optimizing the clinical treatment strategy of locally advanced cervical cancer.Methods:The patients who agreed to use Endostar combined with chemoradiotherapy for locally advanced cervical cancer from 2017 to 2020 were included in this double-center retrospective study.Baseline data such as age,stage,ECOG score,pathological type,and lymph node metastasis of patients in Endostar combined with chemoradiotherapy(E+CRT)group were collected.According to the age and stage of patients in E+CRT group,SPSS 25.0 software was used to match 1:1 case according to the principle of case control to set up a control group.The control group was a simple chemoradiotherapy group(CRT).The patients of two groups were followed up to determine the progression-free survival(PFS)and total survival(OS).The last follow-up time for the two groups was November 1,2021.SPSS 25.0 software was used to analyze the matched data.The continuous variables conforming to the normal distribution were expressed by the mean±standard deviation(x±S).The continuous variables not conforming to the normal distribution were expressed by the median(interquartile interval).The inter-group comparison between E+CRT group and CRT group was performed by t test or Wilcoxon rank sum test.The categorical variables were expressed by example(%),and the inter-group comparison was performed by chi-square(χ~2)Test or Fisher exact probability method.The Kaplan-Meier method and Log-rank test in survival analysis were used to compare the PFS and OS of the two groups,and the PFS and OS of the two groups were analyzed by subgroup.At the same time,the prognostic factors of patients with locally advanced cervical cancer were analyzed by univariate analysis.The factors with P<0.1and clinical significance were included in the Cox regression model,and then the multivariate analysis was performed and the HR value and 95%confidence interval(CI)were calculated,P<0.05 was considered statistically significant.Results:Early treatment response:The CR rates of E+CRT group and CRT group were 48.8%and 26.8%respectively.The difference between the two groups was statistically significant(χ~2=4.20,P<0.05);The ORR of E+CRT group and CRT group was 82.9%and 70.7%respectively.There was no significant difference between the two groups(χ~2=1.71,P>0.05);The DCR of E+CRT group was 92.7%,and that of CRT group was80.5%.There was no significant difference between the two groups(P>0.05).Long-term efficacy:There was no significant difference in the 1-year PFS rate and2-year PFS rate between E+CRT group and CRT group(the 1-year PFS rate:80.5%vs.68.3%;the 2-year PFS rate:68.3%vs.46.3%,P=0.323);Further subgroup analysis of PFS showed that the PFS of the E+CRT group was significantly better than that of the CRT group in patients with locally advanced cervical cancer in stageⅡB(P<0.05).The1-year OS rate and 2-year OS rate of E+CRT group and CRT group were 87.8%vs.82.9%and 73.2%vs.48.8%,respectively.There was no significant difference in OS between the two groups(P=0.154);Further subgroup analysis of OS showed that the difference between each subgroup was not statistically significant(P>0.05).Prognostic factors:stage(P=0.011),ECOG score(P<0.01),and maximum diameter of tumor(P=0.01)were independent predictors of PFS in patients with locally advanced cervical cancer;ECOG score(P<0.01)and maximum diameter of tumor(P=0.026)were independent predictors of OS in locally advanced cervical cancer patients.Safety:The incidence of gradeⅢ-Ⅳbone marrow suppression in E+CRT group was lower than that in CRT group(40%vs.62.5%,χ~2=4.053,P<0.05),there was no significant difference in the incidence of adverse reactions such as nausea/vomiting,radiation enteritis,hypertension,proteinuria and arrhythmia between the two groups(P>0.05).Conclusions:Compared with chemoradiotherapy alone,Endostar combined with chemoradiotherapy for locally advanced cervical cancer showed higher CR rate and good safety.Although the whole group analysis showed that the PFS and OS of Endostar combined with radiotherapy and chemotherapy for locally advanced cervical cancer were not significantly improved,further subgroup analysis showed that the PFS of patients with stageⅡB(FIGO 2009)was significantly improved.The prognosis of locally advanced cervical cancer patients with stageⅡB(FIGO 2009),ECOG score of 0-1 and maximum diameter of tumor<4cm is better.