title: Improved survival with combined gemcitabine and S-1 for locally advanced pancreatic cancer: pooled analysis of three randomized studies.
abstract: BACKGROUND
  The long-term prognosis for localized pancreatic cancer (PC) remains poor. Three randomized trials (GEST phase III, JACCRO PC-01 phase II and GEMSAP phase II) evaluated gemcitabine (Gem) with or without S-1 for patients with metastatic and locally advanced PC. A pooled analysis based on published data examined whether Gem with S-1 (GS) is superior to Gem alone in overall survival (OS) in patients with locally advanced PC.
  
  
  METHODS
  Data were extracted on 193 patients: 31 (JACCRO), 28 (GEMSAP), and 134 (GEST). OS was used for primary endpoint and progression-free survival (PFS) was used for secondary endpoint. A general variance-based method was used to estimate the pooled HR and 95% CI between GS (n = 96) and Gem (n = 97).
  
  
  RESULTS
  Meta-analysis demonstrated that the overall risk of death was significantly different between the two chemotherapies (hazard ratio = 0.673, 95% confidence interval: 0.488-0.929, P = 0.016). The median PFSs for GS and GEM in the JACCRO, GEMSAP, and GEST studies were 12.0, 12.6, and 10.7 months, and 4.1, 8.1, and 6.2 months, respectively (P = 0.001). The random-effect pooled estimate for 165 patients showed the objective response rate (ORR) in the GS group (28.4%) was better in the Gem group (8.3%, P = 0.001).
  
  
  CONCLUSIONS
  GS improved ORR, PFS and OS in patients with locally advanced PC over Gem alone. GS could become one of the front-line chemotherapeutic agents.
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, 573-1010, Japan. yanagimh@hirakata.kmu.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Nakai
authors.forename: Masato
authors.initials: M
authors.lastname: Ozaka
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ikari
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ioka
authors.forename: Sohei
authors.initials: S
authors.lastname: Satoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimokawa
authors.forename: A-Hon
authors.initials: AH
authors.lastname: Kwon
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Isayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012306:Risk; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine
keywords: Gemcitabine with S-1; Locally advanced pancreatic cancer; Pooled analysis