title: Gemcitabine alone or in combination with Cisplatin for advanced biliary tract carcinomas: an overview of clinical evidence.
abstract: OBJECTIVE
  There has been no universally agreed standard chemotherapy regimen for patients with advanced biliary tract carcinomas (BTC). We aimed to fully display and evaluate the clinical evidence for gemcitabine or gemcitabine-cisplatin combination for advanced BTC.
  
  
  METHODS
  Systematic searches were performed to identify relevant randomized controlled trials (RCTs) and uncontrolled trials. Overall survival (OS), progression-free survival (PFS), overall response rates (ORR), tumor control rates (TCR), and toxicity were evaluated. Evidence levels of the results were evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
  
  
  RESULTS
  Results of the eleven gemcitabine-cisplatin trials and ten gemcitabine trials showed both chemotherapy regimens had benefits with reference to mean OS (8.63 vs. 8.79 months), mean PFS (4.86 vs. 4.72 months), pooled ORR (25.3% vs. 19.6%) and TCR (55.2% vs. 53.1%). Two RCTs showed the gemcitabine-cisplatin combination to prolong the mean PFS (mean difference [MD] 2.57, 95%CI 1.69 3.45), substantially increasing the mean OS (MD 3.59, 95% CI 3.48 3.71), and producing a similar effect in ORR (risk ratio [RR] 1.59, 95%CI 1.04 2.43), increasing TCR (RR 1.15, 95%CI 1.02 1.31) compared with gemcitabine alone, with generally manageable grade 3 or 4 adverse events. The evidence level of OS was moderate, and other outcomes (ORR, PFS, TCR, anaemia, neutropenia) were at low evidence levels.
  
  
  CONCLUSIONS
  Available evidence was limited with low quality, which showed that both gemcitabine-cisplatin and gemcitabine alone had clinical activity with acceptable safety profiles, and gemcitabine-cisplatin appeared to be more useful for advanced BTC patients than gemcitabine alone.
authors.affiliation: Shanghai Institute of Digestive Disease, Shanghai Jiaotong University School of Medicine Renji Hospital, Shanghai, China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Sun
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Wang
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001659:Biliary Tract / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D013534:Survival; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine