title: Randomized Phase III study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106).
abstract: OBJECTIVE
  Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis.
  
  
  METHODS
  Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m(2)/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m(2), bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m(2), bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided α of 0.05.
  
  
  RESULTS
  All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm.
  
  
  CONCLUSIONS
  Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.
authors.affiliation: *Department of Medical Oncology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan. kshirao@oita-u.ac.jp.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Goto
authors.forename: Junichiro
authors.initials: J
authors.lastname: Nasu
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016017:Odds Ratio; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil; D008727:Methotrexate
keywords: Phase III study; chemotherapy; gastric cancer; peritoneal metastasis