A Meta-analysis Of The Feasibility Of TOMOX As A First-line Treatment For Advanced Colorectal Cancer

Background: Colorectal cancer(CRC)is a common malignant tumor with high morbidity and mortality among many malignant tumors.Currently,surgery is the treatment of choice for most colorectal cancer patients.In addition,other treatment options,such as radiation,chemotherapy,immunotherapy,and targeted therapy,have provided additional benefits for some patients.However,some patients with advanced stage have a poor prognosis.For patients with advanced colorectal cancer,the prognosis is poor and the options are limited.Chemotherapy or combined chemoradiotherapy are the main treatment methods.The development of new first-line treatment options that are better or have fewer side effects could greatly benefit patients with advanced colorectal cancer.Objective: The efficacy and safety of raltitrexed(Tomudex,TOM,RTX)combined with oxaliplatine(OXA,L-OHP)as first-line treatment of advanced colorectal cancer were evaluated by meta-analysis.Methods: From Pubmed,Embase,Cocharane Library,Web of science,CNKI,CBM,VIP,Wanfang database,a comprehensive search for randomized trials of raltitrexed combined with oxaliplatin(TOMOX)and first-line treatment of colorectal cancer.Select the corresponding literature according to the exclusion criteria.After data extraction,Revman and STATA software were used to To calculate the overall survival(OS),progression-free survival(PFS),objective response rate(ORR)and related chemotherapy of TOMOX regimen and other chemotherapy regimens for first-line treatment of advanced colorectal cancer Meta-analysis of side effects.Results: Finally,19 clinical trials were included,of which 5 were TOMOX single-arm studies and 3 were randomized controlled studies of TOMOX combined with targeted drugs(one of which was chemotherapy alone and combined with targeted drugs).A total of 1446 patients were included,of which There were 774 patients in the TOMOX group,513 patients in the other chemotherapy regimens,77 in the TOMOX combined with targeted drug regimens,and 82 in the other chemotherapy regimens combined with targeted drugs.Meta-analysis results showed that the objective response rate in the TOMOX group was better than that in the FOLFOX group(levofolate + fluorouracil + oxaliplatin): RR = 1.28,95%CI [ 1.02,1.61 ],P = 0.03 and the XELOX group(Oxa Liplatin +capecitabine): RR = 1.54,95%CI [ 1.05 to 2.27 ],P = 0.03;no difference in objective response rate with TOMIRI(raltitrexed + irinotecan): RR =1.18,95 %CI [0.83,1.66],P = 0.35.Overall survival in the TOMOX arm(MD = 2.41,95%CI [0.45,4.36],P = 0.02)was better than other chemotherapy regimens,progression-free survival(MD = 1.39,95%CI [-0.55,3.33],P = 0.16)similar to other chemotherapy regimens.In terms of neurotoxicity,TOMOX was superior to XELOX(RR = 0.62,95%CI [0.39,0.96],P = 0.03);comparable to FOLFOX(RR = 0.80,95%CI [0.53,1.19],P = 0.26);inferior to TOMIRI(RR = 59.12,95% CI [8.02,436.07],P <0.0001);TOMOX was superior in diarrhea(RR = 0.57,95% CI [0.42,0.78],P = 0.0004)For other chemotherapy regimens,there was no difference in liver function(increased transaminases),nausea,vomiting,thrombocytopenia,anemia,neutropenia,stomatitis and mucositis,and weakness compared with other chemotherapy regimens.In the overall analysis,the objective response rate of TOMOX regimen showed: ORR =0.44,95% [ 0.41,0.48];overall survival rate: pooled m OS = 16.75,95%[ 12.66,20.85],pooled m PFS = 7.59,95% [6.55,8.63].In the analysis of efficacy and safety of combined targeted drugs,there was no significant difference in objective response rate between TOMOX combined with Bevac compared with other regimens combined with Bevac:(RR = 1.09,95%CI [ 0.86,1.38 ],P = 0.49);Except for handfoot syndrome(RR = 0.32,95%CI [0.05,0.53],P = 0.002),there was no significant difference in diarrhea,nausea and vomiting,neurotoxicity,anemia,hypertension,and transaminase.Conclusions: According to the analysis of the systematic review,the TOMOX regimen has a definite curative effect in the first-line treatment of advanced colorectal cancer.Compared with other chemotherapy regimens,TOMOX regimen have similar or better curative effect and control of side effects,with mild adverse reactions and good patient tolerance,can be used as a first-line regimen for colorectal cancer promotion.