A Retrospective Study Of Bevacizumab Combined With Chemotherapy In The Treatment Of Recurrent Glioblastoma

Background and Objective:Glioblastoma is an extremely malignant WHO grade IV central nervous system tumor,with an incidence of 3.19/100,000.Even after treatment with the STUPP regimen,the 5 year survival rate was only 9.8%.In 2009,the United States Food and Drug Administration(FDA)approved bevacizumab for the treatment of recurrent high-grade gliomas.However,there is still no consensus on whether the combined application of bevacizumab with other chemotherapy is effective in the treatment of the recurrent high-grade gliomas,and the tumor invasiveness may increase.This retrospective study is designed first to evaluate the clinical efficacy and safety of bevacizumab combined with chemotherapy in the treatment of recurrent glioblastoma,then to compare the efficacy of bevacizumab plus alkylating agents and bevacizumab plus non-alkylating agents and to analyze the predictive value of baseline neutrophil count to the clinical efficacy of bevacizumab.Subjects and methods:1.Subjects:From October 2013 to October 2016,the patients with recurrent glioblastoma were treated in Department of Neurosurgery,Peking Union Medical College Hospital.According to the treatment plan group,signed informed consent before treatment.2.Methods:1)The patients were randomly divided into two groups,who were treated with bevacizumab combined with alkylating agents or non-alkylating agents,and reviewed the head MRI and FLAIR to assess the efficacy of the treatment.2)The response rate,disease control rate,progression free survival,overall survival and adverse events were compared between the two groups.3)COX regression analysis and stepwise backward analysis were used to analyze the correlation between baseline neutrophil number and the effect of bevacizumab treatment.Results:1.The CR of bevacizumab plus alkylating agents group was 10%,PD was 60%,SD was 20%,and CR of non-alkylating agents group was 10%and PD was 50%,SD was 30%.2.The median PFS of the overall study was 5.1 months(95%CI:4.141-5.859),PFS-6 was 40%and median OS was 8.2 months(95%CI:5.820-10.180).The median PFS of alkylating agents group was 4.1 months(95%CI:2.450-5.550),PFS-6 was 20%and the median OS was 6.2 months(95%CI:2.901-9.099);The median PFS of non-alkylating agents group was 6.3 months(95%CI:0-12.198),PFS-6 was 60%and the median OS was 9.1 months(95%CI:6.976-11.024).The difference of PFS and OS between the two groups was statistically significant(P<0.05).3.Baseline neutrophil count was correlated with overall survival after bevacizumab treatment with a 5 x 10^9/L boundary.Bevacizumab combined with chemotherapy may be better.More cases should be included as predictors.Conclusion:1.Bevacizumab combined with chemotherapy has a low incidence of severe adverse events in recurrent glioblastoma and is generally well tolerated and safe.2.Bevacizumab combined with non-alkylating agents(irinotecan)therapy is a preferred option for chemotherapy in relapsed malignant gliomas.3.the baseline neutrophil count could be a predictor of bevacizumab efficacy.