title: Phase II study of sequential methotrexate and 5-fluorouracil chemotherapy against peritoneally disseminated gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial.
abstract: BACKGROUND
  The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting.
  
  
  METHODS
  The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration.
  
  
  RESULTS
  Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%).
  
  
  CONCLUSIONS
  Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.
authors.affiliation: Department of Internal Medicine, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Takekazu
authors.initials: T
authors.lastname: Yamao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Ikeda
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwase
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001201:Ascites / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate