title: Efficacy and safety of gemcitabine-fluorouracil combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Gemcitabine (GEM) is the standard first-line chemotherapy that provides limited clinical benefits for patients with locally advanced/metastatic pancreatic adenocarcinoma (LA/MPC). However, the fluorouracil derivatives (CAP and S-1) show promising efficacy in these patients. This study compared the efficacy and safety of GEM with GEM plus fluorouracil drugs in the treatment of LA/MPC.
  
  
  METHODS
  Pubmed, EMBASE and Cochrane Library databases were searched for relevant randomized controlled trials published on or before January 2014. The Cochrane Collaboration's tool was used to assess the risk of bias in randomized trials. The primary end point was overall survival (OS); the secondary end points were one-year survival rate, objective response rate (ORR) and toxicity rates (TRs).
  
  
  RESULTS
  A total of 8 randomized controlled trials involving 2,126 patients were included in the systematic evaluation. The results showed that OS was significantly improved (HR 0.83, P<0.01; HR 0.87, P = 0.03; HR 0.80, P = 0.01; respectively) and ORR was significantly increased (OR 0.51, P<0.01; OR 0.66, P = 0.03; OR 0.35, P<0.01; respectively) in the GEM+5-FU/CAP/S-1, GEM+CAP and GEM+S-1 groups compared to the GEM alone group. In addition, the one-year survival rate was significantly increased (OR 0.78 P = 0.01; OR 0.47, P = 0.04; respectively) in the GEM+5-FU/CAP/S-1 and GEM+S-1 groups compared to the GEM alone group. The frequency of grade 3/4 TRs were higher in GEM+5-FU/CAP/S-1 group, the significant increase of grade 3/4 neutropenia, thrombocytopenia and diarrhea were observed.
  
  
  CONCLUSIONS
  GEM combined with fluorouracil drugs significantly improved OS and increased one-year survival rate and ORR compared to GEM alone in LA/MPC patients. GEM combined with fluorouracil drugs may be considered as an acceptable alternative treatment for LA/MPC patients.
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Digestive Diseases Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Digestive Diseases Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhen
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Digestive Diseases Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Digestive Diseases Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Cao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine
references.citation: Ann Oncol. 2003 Jan;14(1):97-104
references.pmid: 12488300
references.citation: Cancer Res Treat. 2012 Jun;44(2):127-32
references.pmid: 22802751
references.citation: J Clin Oncol. 2013 Jan 1;31(1):23-9
references.pmid: 23213101
references.citation: J Clin Oncol. 2007 May 20;25(15):1960-6
references.pmid: 17452677
references.citation: Cancer Res Treat. 2008 Mar;40(1):22-6
references.pmid: 19688061
references.citation: J Clin Oncol. 2002 Jul 15;20(14):3130-6
references.pmid: 12118027
references.citation: Eur J Cancer. 2013 Feb;49(3):593-603
references.pmid: 22989511
references.citation: Expert Opin Investig Drugs. 2009 Mar;18(3):335-48
references.pmid: 19243284
references.citation: J Clin Oncol. 2009 Nov 20;27(33):5513-8
references.pmid: 19858379
references.citation: J Clin Oncol. 1997 Jun;15(6):2403-13
references.pmid: 9196156
references.citation: Jpn J Clin Oncol. 2010 May;40(5):432-41
references.pmid: 20147334
references.citation: Stat Med. 1998 Dec 30;17(24):2815-34
references.pmid: 9921604
references.citation: N Engl J Med. 2013 Oct 31;369(18):1691-703
references.pmid: 24131140
references.citation: Br J Cancer. 2006 Apr 24;94(8):1107-15
references.pmid: 16622436
references.citation: Jpn J Clin Oncol. 2009 Jan;39(1):2-15
references.pmid: 19052037
references.citation: J Clin Oncol. 2002 Aug 1;20(15):3270-5
references.pmid: 12149301
references.citation: J Hematol Oncol. 2011 Mar 26;4:11
references.pmid: 21439076
references.citation: Trials. 2007 Jun 07;8:16
references.pmid: 17555582
references.citation: J Clin Oncol. 2007 Jun 1;25(16):2212-7
references.pmid: 17538165
references.citation: J Cancer Res Clin Oncol. 2011 Jun;137(6):927-38
references.pmid: 20936301
references.citation: J Hematol Oncol. 2009 Mar 16;2:13
references.pmid: 19291303
references.citation: Br J Cancer. 2006 Jun 5;94(11):1575-9
references.pmid: 16721372
references.citation: World J Gastroenterol. 2012 Sep 21;18(35):4944-58
references.pmid: 23002368
references.citation: Br J Cancer. 2012 Jun 5;106(12):1934-9
references.pmid: 22555398
references.citation: World J Gastroenterol. 2006 Nov 21;12(43):6973-81
references.pmid: 17109519
references.citation: J Clin Oncol. 2002 Jan 1;20(1):160-4
references.pmid: 11773165
references.citation: Cancer. 2007 Aug 1;110(3):525-33
references.pmid: 17577216
references.citation: BMJ. 2009 Jul 21;339:b2535
references.pmid: 19622551
references.citation: Br J Cancer. 2005 Jul 25;93(2):185-9
references.pmid: 15986036
references.citation: Pancreas. 2013 Apr;42(3):511-5
references.pmid: 23462324
references.citation: BMJ. 2011 Oct 18;343:d5928
references.pmid: 22008217
references.citation: Cancer Chemother Pharmacol. 2012 May;69(5):1197-204
references.pmid: 22249272
references.citation: J Clin Oncol. 2013 May 1;31(13):1640-8
references.pmid: 23547081