title: Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer.
abstract: OBJECTIVE
  There are a large number of randomized controlled trials involving chemotherapy in the management of advanced pancreatic cancer. Several chemotherapeutic agents, either alone or in combination with other chemotherapy or novel agents, have been used. The aim of these meta-analyses was to examine the different therapeutic approaches, and the comparisons examined were as follows: chemotherapy versus best supportive care; fluorouracil (FU) versus FU combination chemotherapy; gemcitabine versus FU; and gemcitabine versus gemcitabine combination chemotherapy.
  
  
  METHODS
  Relevant trials were identified by searching databases, trial registers, and conference proceedings. The primary end point was overall survival.
  
  
  RESULTS
  One hundred thirteen randomized controlled trials were identified, of which 51 trials involving 9,970 patients met the inclusion criteria. Chemotherapy improved survival compared with best supportive care (hazard ratio [HR] = 0.64; 95% CI, 0.42 to 0.98). FU-based combination chemotherapy did not result in better overall survival compared with FU alone (HR = 0.94; 95% CI, 0.82 to 1.08). There was insufficient evidence of a survival difference between gemcitabine and FU, but the wide CI includes clinically important differences in both directions, making a clear conclusion difficult (HR = 0.75; 95% CI, 0.42 to 1.31). Survival was improved after gemcitabine combination chemotherapy compared with gemcitabine alone (HR = 0.91; 95% CI, 0.85 to 0.97).
  
  
  CONCLUSIONS
  There was a significant survival benefit for chemotherapy over best supportive care and gemcitabine combinations over gemcitabine alone. This supports the use of gemcitabine-based combination chemotherapy in the treatment of advanced pancreatic cancer.
authors.affiliation: Cancer Research UK Liverpool Cancer Trials Unit and Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Asma
authors.initials: A
authors.lastname: Sultana
authors.forename: Catrin Tudur
authors.initials: CT
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Naureen
authors.initials: N
authors.lastname: Starling
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D009362:Neoplasm Metastasis; D017063:Outcome Assessment, Health Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine