title: The efficacy of adjuvant immunochemotherapy with OK-432 after curative resection of gastric cancer: an individual patient data meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  OK-432 has been used as a cancer treatment for 40 years, and the immunostimulatory effects of OK-432 therapy have been intensely investigated in Japan. Recently, it has received attention as a possible booster for cancer vaccine treatments. Our previous meta-analysis based on summary measures revealed a significant improvement in the survival of patients with curatively resected gastric cancer. However, it is impossible to exclude the possibility of bias due to several prognostic factors.
  
  
  METHODS
  We collected individual data for patients with stage III or stage IV gastric cancer after curative resection from 14 trials that were identified in a previous meta-analysis. Immunochemotherapy with OK-432 was compared with treatment with standard chemotherapy on an intention-to-treat basis. The primary end point was overall survival. Stratified survival analyses were performed with the trial as the stratification factor. Subgroup analyses were also performed according to the potential prognostic factors, which included pathological factors, splenectomy, and delayed-type hypersensitivity.
  
  
  RESULTS
  There were 796 and 726 patients in the OK-432 and control groups, respectively. The median overall survival was 42.6 months for the OK-432 group and 32.3 months for the control group. The overall hazard ratio was 0.88 (95 % confidence interval 0.77-1.00, p = 0.050). No factor showed a statistically significant interaction in the subgroup analyses.
  
  
  CONCLUSIONS
  The results suggest that immunochemotherapy treatment with OK-432 could have a borderline significant effect for patients with stage III or stage IV gastric cancer after curative resection.
authors: Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan. mari@yokohama-cu.ac.jp.|, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan. mari@yokohama-cu.ac.jp.
authors: Mari S
authors: MS
authors: Oba
authors: Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Satoshi
authors: S
authors: Teramukai
authors: Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Ohashi
authors: Department of Surgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors: Kenji
authors: K
authors: Ogawa
authors: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Yoshihiko
authors: Y
authors: Maehara
authors: Tokai Central Hospital, Kakamigahara, Japan.
authors: Junichi
authors: J
authors: Sakamoto
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D010844:Picibanil
keywords: Adjuvant immunochemotherapy; Gastric cancer; Individual patient data; Meta-analysis; OK-432