Optimal treatment strategy of first-line oxaliplatin (Oxa)-containing therapy in metastatic colorectal cancer (mCRC): A trial-level meta-analysis

Background ThetreatmentstrategyofOxa-containingtherapy,whichiscomprisedof inductiontherapy(IT)followedbymaintenancetherapywithoutOxa,andthen considering Oxa reintroduction (ReOxa), is recognized as an option in mCRC patients because of particularly Oxa induced chronic peripheral neuropathy. However, the optimaldurationofITandnumber(No.)ofmaintenancedrugs(MDs)andtheneedfor ReOxa are unclear. Methods:WeconductedaliteraturesearchofphaseIIandIIItrialsoffirst-lineOxa- containing chemotherapy including maintenance therapy for mCRC that were presented up to March 2016, and investigated relationships between median overall survival(OS)anddurationofIT,No.ofMDs,andReOxarateusingcorrelationanalysis and weighted multivariate regression analysis. Results:Twenty-seventreatmentarmswereidentifiedamong18trialsandasamplesize of 3,109 patients was analyzed. IT was 11 chemotherapy alones and 16 chemotherapy + targetedagents.MediandurationofITwas18weeks(range,12to27).No.ofMDswas0 in 8 treatment arms, 1 (FU ortargeted agent) in11 treatment arms, and 2 (FU + targeted agent) in 9 treatment arms. Median ReOxa rate was 30.9% (range, 0 to 100). MedianOSwas23.2months(range,15.8to31.0).DurationofITwasweaklycorrelated withOS(Spearman'spartialcorrelationcoefficient,r=0.14).No.ofMDswasmoderately correlationwithOS(r=0.60).ReOxaratewasweaklycorrelationwithOS(r=0.07).In multivariate regression analysis, No. of MDs was significantly correlated with OS (P = 0.004). There was a significant interaction between duration ofIT and No. ofMDs (P = 0.014). The longest predicted OS was the treatment strategy comprised ofIT for 12 weeks and 2 MDs when IT for 12-24 weeks and 0-2 MDs were applied to the model. Conclusions: ThestrongestcorrelationwithimprovementofOSwasthemaintenance therapy using FU + targeted agent. The optimal treatment strategy of Oxa-containing therapymaybecomprisedofITfor12weeksfollowedbytwoMDs,notconsidering ReOxainfirst-linesettingformCRC. Legal entity responsible for the study National university corporation Funding Division ofGastroenterology Disclosure All authors have declared no conflicts ofinterest.