title: Efficacy and safety of chemotherapy with or without targeted therapy in biliary tract cancer: A meta-analysis of 7 randomized controlled trials.
abstract: The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis. The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87; 95% CI: 1.37-2.57; P=0.000), but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63; 95% CI:-0.45-1.72; P=0.26] and overall survival (OS) (MD=-0.67; 95% CI:-2.54-1.20; P=0.49). In the sub analysis, better ORR was obtained with the addition of EGFR (OR=1.75; 95% CI: 1.20-2.56; P=0.004) and VEGFR (OR=2.5; 95% CI: 1.28-4.87; P=0.007) targeted therapy. Furthermore, the sub analysis of EGFR target showed an significant improvement on PFS (MD=1.36; 95% CI: 0.29-2.43; P=0.01). No significant differences were observed in the incidences of neutropenia (OR=1.37; 95% CI: 0.89-2.12), thrombocytopenia (OR=1.40; 95% CI: 0.83-2.39), anemia (OR=1.21; 95% CI: 0.62-2.38), peripheral neuropathy (OR=1.52; 95% CI: 0.81-2.88), increased AST/ALT (OR=1.40; 95% CI: 0.82-2.39) as well as fatigue (OR=1.65; 95% CI: 0.96-2.84) in either of the treatment groups. In conclusion, better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present meta-analysis without the cost of increased unacceptable toxicities, but regretfully not for the OS. The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS. Otherwise, there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone. Given the paucity of favorable data, we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, 063000, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xiao
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
authors.forename: Ling-Hua
authors.initials: LH
authors.lastname: Tan
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
authors.forename: Lu-Ting
authors.initials: LT
authors.lastname: Wang
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Qu
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China. 13874925173@163.com.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Duan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: biliary tract cancer; chemotherapy; cholangiocarcinoma; gallbladder cancer; targeted therapy