title: Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial).
abstract: OBJECTIVE
  We compared biweekly irinotecan plus cisplatin (BIRIP) with irinotecan alone as the second-line chemotherapy (SLC) for advanced gastric cancer (AGC).
  
  
  METHODS
  Patients with metastatic or recurrent gastric cancer refractory to S-1-based first-line chemotherapy were randomly assigned to receive BIRIP (irinotecan 60mg/m(2) plus cisplatin 30mg/m(2), every 2weeks) or irinotecan alone (irinotecan 150mg/m(2), every 2weeks). The primary end-point was to show the superiority of BIRIP to irinotecan in terms of progression free survival (PFS).
  
  
  RESULTS
  130 patients were enrolled. PFS was significantly longer in the BIRIP group (3.8months [95% confidence interval (CI) 3.0-4.7]) than in the irinotecan group (2.8months [2.1-3.3]; hazard ratio 0.68, 95% CI 0.47-0.98; P=0.0398). Median overall survival was 10.7months in the BIRIP group and 10.1months in the irinotecan group (HR 1.00, 95% CI 0.69-1.44, P=0.9823). The objective response rate was 22% in the BIRIP group and 16% in the irinotecan group (P=0.4975). However, the disease control rate was significantly better in the BIRIP group (75%) than in the irinotecan group (54%, P=0.0162). The incidences of grade 3 or worse adverse events did not differ between the two groups. Any grade elevation of serum creatinine was more common in the BIRIP group (25% versus 8%, P=0.009), but any grade diarrhoea (17% versus 42%, P=0.002) was more common in the irinotecan group.
  
  
  CONCLUSIONS
  BIRIP significantly prolonged PFS as compared with irinotecan alone and was tolerated as SLC, but did not demonstrate the survival benefit in this trial.
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Kanagawa, Japan. Electronic address: k.higu@kitasato-u.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Kanagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Department of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Gastroenterology, Gunma Prefectural Cancer Center, Gunma, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hosaka
authors.affiliation: Department of Chemotherapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center Hospital, Kanagawa, Japan.
authors.forename: Norisuke
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology, Showa General Hospital, Tokyo, Japan.
authors.forename: Yuiti
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Division of Gastroenterology, University of Tsukuba Hospital, Ibaraki, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Moriwaki
authors.affiliation: Department of Gastroenterology, Ibaraki Prefectural Central Hospital and Cancer Center, Ibaraki, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amagai
authors.affiliation: Department of Gastroenterology, Showa University Toyosu Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekikawa
authors.affiliation: Division of Oncology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Sakuyama
authors.affiliation: Division of Digestive and General Surgery, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Kanagawa, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Kanagawa, Japan.
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Kanagawa, Japan.
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D003404:Creatinine; D002945:Cisplatin; D002166:Camptothecin
keywords: Cisplatin; Gastric cancer; Irinotecan; Second-line chemotherapy