title: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data.
abstract: OBJECTIVE
  This systematic review and meta-analysis were performed to assess the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer.
  
  
  METHODS
  Randomized phase II and III clinical trials on first-line chemotherapy in advanced gastric cancer were identified by electronic searches of Medline, Embase, the Cochrane Controlled Trials Register, and Cancerlit; hand searches of relevant abstract books and reference lists; and contact to experts. Meta-analysis was performed using the fixed-effect model. Overall survival, reported as hazard ratio (HR) with 95% CI, was the primary outcome measure.
  
  
  RESULTS
  Analysis of chemotherapy versus best supportive care (HR = 0.39; 95% CI, 0.28 to 0.52) and combination versus single agent, mainly fluorouracil (FU) -based chemotherapy (HR = 0.83; 95% CI = 0.74 to 0.93) showed significant overall survival benefits in favor of chemotherapy and combination chemotherapy, respectively. In addition, comparisons of FU/cisplatin-containing regimens with versus without anthracyclines (HR = 0.77; 95% CI, 0.62 to 0.95) and FU/anthracycline-containing combinations with versus without cisplatin (HR = 0.83; 95% CI, 0.76 to 0.91) both demonstrated a significant survival benefit for the three-drug combination. Comparing irinotecan-containing versus nonirinotecan-containing combinations (mainly FU/cisplatin) resulted in a nonsignificant survival benefit in favor of the irinotecan-containing regimens (HR = 0.88; 95% CI, 0.73 to 1.06), but they have never been compared against a three-drug combination.
  
  
  CONCLUSIONS
  Best survival results are achieved with three-drug regimens containing FU, an anthracycline, and cisplatin. Among these, regimens including FU as bolus exhibit a higher rate of toxic deaths than regimens using a continuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU.
authors.affiliation: First Department of Medicine, Coordinating Centre for Clinical Trials, and Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Wagner
authors.forename: Wilfried
authors.initials: W
authors.lastname: Grothe
authors.forename: Johannes
authors.initials: J
authors.lastname: Haerting
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kleber
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Fleig
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D013274:Stomach Neoplasms / Q000188:drug therapy*