title: The Efficacy and Safety of First-line Chemotherapy in Advanced Esophagogastric Cancer: A Network Meta-analysis.
abstract: A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and safety of first-line chemotherapy using Network meta-analysis (NMA).
  
  
  
  Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin [C] and oxaliplatin [Ox]), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs).
  
  
  
  The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx.
  
  
  
  Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Emil
authors: E
authors: Ter Veer
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Nadia
authors: N
authors: Haj Mohammad
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Gert
authors: G
authors: van Valkenhoef
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Lok Lam
authors: LL
authors: Ngai
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Rosa M A
authors: RMA
authors: Mali
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Maarten C
authors: MC
authors: Anderegg
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Martijn G H
authors: MGH
authors: van Oijen
authors: Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV).
authors: Hanneke W M
authors: HWM
authors: van Laarhoven
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004943:Esophagogastric Junction; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008727:Methotrexate / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; C080625:taxane; D010094:Oxonic Acid; D000069287:Capecitabine; D000077146:Irinotecan; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin; D008727:Methotrexate