title: Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study.
abstract: OBJECTIVE
  The present phase III study was designed to investigate the noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with gemcitabine alone with respect to overall survival.
  
  
  METHODS
  The participants were chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer. Patients were randomly assigned to receive only gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle).
  
  
  RESULTS
  In the total of 834 enrolled patients, median overall survival was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1 months in the gemcitabine plus S-1 group. The noninferiority of S-1 to gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P < .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were generally well tolerated, although hematologic and GI toxicities were more severe in the gemcitabine plus S-1 group than in the gemcitabine group.
  
  
  CONCLUSIONS
  Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.
authors.affiliation: Taiho Pharmaceutical, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ioka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohkawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Akira
authors.initials: A
authors.lastname: Fukutomi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sugimori
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Shimamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitano
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Jen-Shi
authors.initials: JS
authors.lastname: Chen
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Akihiro
authors.initials: A
authors.lastname: Funakoshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Hatori
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D016019:Survival Analysis; D013624:Taiwan; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine