The Clinical Research Of GEMOX Or GEMOX Plus Molecular Targeted Drugs In Patients With Biliary Tract Cancer

Objectives: The aim of this study was to determine the efficacy and safety profile of GEMOX or GEMOX plus molecular targeted drugs in patients with biliary tract cancer(BTC).Methods: Retrospective analysis was used to determine the efficacy difference between gemcitabine plus platinum-based drugs and gemcitabine plus5FU-based drugs in BTC patients treated in Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine,through which the theoretical foundation of GEMOX was established.Another retrospective analysis was performed to identify the correlation between polymorphism of DNA-repair-related and detoxifying-enzyme-related genes(ERCC1?ERCC2?XRCC1?GSTP1)and GEMOX's clinical efficacy.After that,we enrolled BTC patients with ERCC1 C8092 A and ERCC2 A2298 C wild type prospectively for GEMOX treatment to further verify the the correlation between polymorphism and GEMOX's clinical efficacy.For GEMOX-resistant patients,GEMOX plus molecular targeted drugs or FOLFIRINOX were used to identify the result of the second-line treatment.Results: In retrospective analysis,9 of 18 BTC patients with ERCC1 C8092 A wild type had partial response(PR),9 of 21 BTC patients with ERCC2 A2282 C wild type had PR.Both gene-wild-type groups showed statistically significant difference respectively with gene-mutant-type groups(P=0.015 and P=0.012).In prospective study,after at least 2cycles of GEMOX treatment,the median progression-free survival(PFS)was 4.0months in gene-wild-type group and 3.0 months in gene-mutant-type group(P<0.05).The median overall survival(OS)was 11.0 months in gene-wild-type group and 8.0 months in gene-mutant-type group(P<0.05).Cetuximab combined with GEMOX did not significantly improve the ORR of the patients(P>0.05),whereas Trastuzumab combined with GEMOX demonstrated activity in those Her-2 positive patients.FOLFIRINOX as second-line therapy showed promising results in locally advanced or metastatic BTC patients.Conclusions: GEMOX as first-line therapy for BTC patients with ERCC1 C8092 A and ERCC2 A2298 C wild type showed promising results.Trastuzumab combined with GEMOX demonstrated activity in Her-2(+)patients.FOLFIRINOX is recommended as second-line therapy for PD patients after GEMOX treatment.