title: Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.
abstract: BACKGROUND
  We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC).
  
  
  METHODS
  In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease.
  
  
  RESULTS
  Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%).
  
  
  CONCLUSIONS
  SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS.
  
  
  BACKGROUND
  JapicCTI-101021.
authors.affiliation: Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo. Electronic address: yayamada@ncc.go.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Sagamihara.
authors.forename: K
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Surgery, Osaka General Medical Center, Osaka.
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki.
authors.forename: M
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Division of Gastrointestinal Oncology and Digestive Endoscopy, National Cancer Center Hospital East, Kashiwa.
authors.forename: N
authors.initials: N
authors.lastname: Fuse
authors.affiliation: Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka.
authors.forename: N
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama.
authors.forename: T
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama.
authors.forename: K
authors.initials: K
authors.lastname: Amagai
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of JFCR, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Chin
authors.affiliation: Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya.
authors.forename: Y
authors.initials: Y
authors.lastname: Niwa
authors.affiliation: Department of Medical Oncology, Kochi Health Sciences Center, Kochi.
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Surgery, Sakai City Hospital, Sakai.
authors.forename: H
authors.initials: H
authors.lastname: Imamura
authors.affiliation: Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi.
authors.forename: M
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun.
authors.forename: H
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Division of Clinical Oncology, Jichi Medical University, Shimotsuke.
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Division of Gastroenterology, Saitama Cancer Center, Kita-adachi-gun.
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Medical Oncology, National Hospital Organization Kyoto Medical Center, Kyoto.
authors.forename: H
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Clinical Trial Promotion Department, Chiba Cancer Center, Chiba.
authors.forename: S
authors.initials: S
authors.lastname: Hironaka
authors.affiliation: Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama.
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya.
authors.forename: H
authors.initials: H
authors.lastname: Miwa
authors.affiliation: Faculty of Engineering, Tokyo University of Science, Tokyo.
authors.forename: C
authors.initials: C
authors.lastname: Hamada
authors.affiliation: Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Hyodo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin
keywords: S-1; advanced gastric cancer; cisplatin; oxaliplatin; phase III study