Network Meta-analysis Of The Clinical Treatment Of Cancer With Paclitaxel Drug Delivery System

Taxanes agents and related preparations were important antitumor drugs,and were widely used in clinical medicine and research.In order to explore the efficacy and safety of Taxanes agents on tumor,this study intended to include clinical research and compare them in network meta-analysis,and so provide evidence for paclitaxel dosage form design.First,we comprehensively searched Embase,MEDLINE,Cochrane library,ClinicalTrials,conference papers and grey literatures.A total of 35103 studies were obtained,and 31535 were left after duplicate removal.Then screened according to the PICOS and fianlly included 29 clinical randomized controlled trials,which included 14098 cancer patients.Taxanes agents contained paclitaxel injection,docetaxel,albumin-bound paclitaxel,paclitaxel polymer micelles,paclitaxel liposomes,paclitaxel cationic liposomes.The quality of the included studies were evaluated in Revman,in which the quality was defined as high risk,unclear risk and low risk according to cochrane criterion.Among the included trials,10 reported the details of randomization methods,3 were single-blind,8 were allocation concealment,and 15 articles judged potential conflicts of interest.The efficacy contained overall survival(OS),progression free survival(PFS),progression disease(PD),and objective response(OR).The safety contained neutrophils,nausea and vomiting.Network meta-analysis was performed using R software through gemtc package and OpenBUGS package,chose the random effect model,the parameter was n.adapt=5000,n.iter=50000.The convergence of all the outcome indexes were satisfactory.All I2 values met the requirements of model heterogeneity evaluation,except C vs A and D vs A in OS-1 years,C vs B in PFS-1 years,B vs A and C vs B in PFS-3 years,and B vs A in objective response.C vs A of neutropenia,C vs B for nausea and vomiting.Because of substantial heterogeneity,the random effects model was chosen.All p values met the requirements of model consistency results,except C vs A and C vs B for OS-1 years,and D vs C for objective response.The differences in the D vs C of the objective response were statistically significant.The rank probability showed that paclitaxel polymer micelles,albumin-bound paclitaxel,docetaxel,and paclitaxel injections were ranked first in OS-1,OS-3,PFS-1,and PFS-3 respectively.The best objective response was the paclitaxel polymer micelles,Paclitaxel liposome was the best effect for progression disease.For the safety of chemotherapy,neutrophils and nausea and vomiting caused by paclitaxel liposomes were better than the others.Comprehensively,compared with paclitaxel injection,docetaxel were similar in objective response,but could significantly reduce neutropenia.Albumin-binding paclitaxel had similar efficacy in long-term efficacy,the objective response was better than paclitaxel injection.Paclitaxel polymer micelles had similar efficacy in long-term efficacy and the objective response was better than paclitaxel injection.The reaction to nausea and vomiting were small.The objective response of paclitaxel liposomes were significantly worse than paclitaxel injection.It could reduce the incidence of nausea and vomiting.The objective response of paclitaxel cationic liposomes were significantly worse than paclitaxel injection.Paclitaxel cationic liposomes reduced neutropenia.