title: Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05).
abstract: BACKGROUND
  In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC.
  
  
  METHODS
  Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS).
  
  
  RESULTS
  From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group.
  
  
  CONCLUSIONS
  The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.
authors.affiliation: Department of Gastroenterological and Transplant Surgery, Hiroshima University Hospital, Hiroshima.
authors.forename: K
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Digestive Surgery, Nihon University School of Medicine, Tokyo. Electronic address: masashi.fujii@gioncology.jp.
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Surgery, Osaka National Hospital, Osaka.
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama.
authors.forename: C
authors.initials: C
authors.lastname: Kunisaki
authors.affiliation: Department of Clinical Oncology, Kobe City Medical Center General Hospital, Kobe.
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu.
authors.forename: N
authors.initials: N
authors.lastname: Matsuhashi
authors.affiliation: Department of Surgery, Hakodate Goryokaku Hospital, Hakodate.
authors.forename: A
authors.initials: A
authors.lastname: Takagane
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi.
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Department of Surgery, Sakai City Hospital, Sakai.
authors.forename: T
authors.initials: T
authors.lastname: Kawase
authors.affiliation: Department of Digestive Surgery, Nihon University School of Medicine, Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Kochi
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe.
authors.forename: Y
authors.initials: Y
authors.lastname: Kakeji
authors.affiliation: Devision of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo.
authors.forename: W
authors.initials: W
authors.lastname: Ichikawa
authors.affiliation: Division of Gastroenterology, Cancer Institute Hospital of JFCR, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Chin
authors.affiliation: Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka.
authors.forename: M
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Japan Clinical Cancer Research Organization, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; 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*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin
keywords: S-1; gastric cancer; irinotecan; second-line chemotherapy