title: Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer.
abstract: BACKGROUND
  This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC).
  
  
  METHODS
  Ninety patients were randomised to a standard dose of wPTX (80 mg m(-2)) or an escalated dose of wPTX (80-120 mg m(-2)) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8.
  
  
  RESULTS
  The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34).
  
  
  CONCLUSIONS
  Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P<0.3); however, it did not show a significantly longer OS. Progression-free survival was significantly better with dose escalation.
authors.affiliation: 1] Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan [2] Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shitara
authors.affiliation: Department of Gastroenterology, Hokkaido University Hospital, Hokkaido, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yuki
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Tahahari
authors.affiliation: Department of Gastroenterology, Sapporo City General Hospital, Hokkaido, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kondo
authors.affiliation: Department of Clinical Oncology, Saint Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
authors.affiliation: Cancer Chemotherapy Center, Osaka Medical College, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kii
authors.affiliation: Department of Medical Oncology, KKR Sapporo Medical Center, Tonan Hospital, Hokkaido, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology, Nagoya Kyoritsu Hospital, Aichi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Utsunomiya
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Department of Gastroenterology and Hematology, University of Toyama, Toyama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hosokawa
authors.affiliation: Department of Medical Oncology, Hirosaki University, Aomori, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ishiguro
authors.affiliation: Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Sakai
authors.affiliation: Department of Clinical Trial Promotion, Chiba Cancer Center, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hironaka
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Oze
authors.affiliation: 1] Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan [2] Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Muro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel