title: Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial).
abstract: BACKGROUND
  Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy.
  
  
  METHODS
  The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum.
  
  
  RESULTS
  Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age.
  
  
  CONCLUSIONS
  The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.
authors.affiliation: Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan. sur001@poh.osaka-med.ac.jp.|Tanigawa Memorial Hospital, 16-59 Kasuga 1-Cho-Me, Ibaraki, Osaka, 567-0031, Japan. sur001@poh.osaka-med.ac.jp.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tanigawa
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
authors.affiliation: Division of Digestive Surgery, Cancer Center Institute Ariake Hospital, Tokyo, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Ohyama
authors.affiliation: Departmet of Surgery, Kitasato University, Sagamihara, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakuramoto
authors.affiliation: Division of Surgery, Tochigi Cancer Center, Utsunomiya, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Inada
authors.affiliation: Second Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.affiliation: Department of Surgery, Faculty of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Division of Surgery, Ageo Central General Hospital, Ageo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Omura
authors.affiliation: Division of Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Misawa City Hospital, Aomori, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Division of Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nashimoto
authors.affiliation: Division of Digestive Surgery, Cancer Center Institute Ariake Hospital, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Division of Medical Oncology, Cancer Center Institute Ariake Hospital, Tokyo, Japan.
authors.forename: Keisho
authors.initials: K
authors.lastname: Chin
authors.affiliation: Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nomura
authors.affiliation: Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
authors.forename: San-Woong
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Kitasato University, Sagamihara, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Surgery, Nihon University of School of Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujii
authors.affiliation: The Japan Clinical Cancer Research Organization, Tokyo, Japan.
authors.forename: Toshifusa
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality* / Q000601:surgery; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil
keywords: Appropriate cutoff values; Chemosensitivity test; Nonresponder; Relapse-free survival; Responder