title: Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407).
abstract: BACKGROUND
  This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine.
  
  
  METHODS
  In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m(2)/day, days 1-5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m(2) followed by bolus 5-FU at 600 mg/m(2) with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m(2)) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival.
  
  
  RESULTS
  One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57-1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38-0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm.
  
  
  CONCLUSIONS
  As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Shikoku Cancer Center, 160 Minami-Umenomoto Kou, Matsuyama, Ehime, 791-0280, Japan. tnishina@shikoku-cc.go.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.affiliation: Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hamamoto
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Division of Gastroenterology, Saitama Cancer Center, Kita-adachi-gun, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawai
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Norisuke
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amagai
authors.affiliation: JCOG Data Center/Operations Office, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.affiliation: JCOG Data Center/Operations Office, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, Yufu, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.affiliation: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000069287:Capecitabine; D000077146:Irinotecan; D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: 5-Fluorouracil; Gastric cancer; Paclitaxel; Peritoneal metastasis; Phase II study