title: Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS).
abstract: BACKGROUND
  Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed.
  
  
  METHODS
  This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382).
  
  
  RESULTS
  Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3.
  
  
  CONCLUSIONS
  SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: M-H
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Baba
authors.affiliation: Department of Hemato-oncology, Yeungnam University Hospital, Daegu.
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Y I
authors.initials: YI
authors.lastname: Park
authors.affiliation: Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki.
authors.forename: N
authors.initials: N
authors.lastname: Boku
authors.affiliation: Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Hyodo
authors.affiliation: Biometric Research Branch, National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: B-H
authors.initials: BH
authors.lastname: Nam
authors.affiliation: Department of Gastrointestinal and Medical Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Esaki
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: C
authors.initials: C
authors.lastname: Yoo
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: B-Y
authors.initials: BY
authors.lastname: Ryoo
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju.
authors.forename: E-K
authors.initials: EK
authors.lastname: Song
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Gwangju.
authors.forename: S-H
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School Medicine, Seoul.
authors.forename: W K
authors.initials: WK
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul.
authors.forename: S H
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang.
authors.forename: D Y
authors.initials: DY
authors.lastname: Zang
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea.
authors.forename: D B
authors.initials: DB
authors.lastname: Shin
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: S R
authors.initials: SR
authors.lastname: Park
authors.affiliation: Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima.
authors.forename: K
authors.initials: K
authors.lastname: Shinozaki
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Minato-ku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takano
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ykkang@amc.seoul.kr.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin
keywords: S-1; chemotherapy; cisplatin; gastric cancer