title: Phase I study of fixed dose rate infusion of gemcitabine in patients with unresectable pancreatic cancer.
abstract: OBJECTIVE
  The purpose of this study was to determine the feasible dose of gemcitabine when administered as a fixed dose rate infusion (10 mg/m(2)/min) on a weekly schedule to Japanese patients with unresectable advanced pancreatic cancer.
  
  
  METHODS
  Patients were required to have histologically or cytologically proven locally advanced or metastatic pancreatic cancer for which they had received no previous chemotherapy. Gemcitabine was administered intravenously weekly for three consecutive weeks every 4 weeks. Patients at three dose levels were scheduled to receive escalating doses of gemcitabine: 1000 mg/m(2) over 100 min (Level 1), 1200 mg/m(2) over 120 min (Level 2) and 1500 mg/m(2) over 150 min (Level 3).
  
  
  RESULTS
  A total of 16 patients were enrolled in this study between December 2003 and September 2004. Maximum-tolerated dose was not reached during the first course. Dose-limiting toxicity was Grade 4 neutropenia. Grade 3 or 4 neutropenia was observed at Level 3 in all six patients in the first course, and administration of gemcitabine on Day 8 or 15 was skipped in all six patients. Non-hematologic toxicity was mild and the most common symptoms were anorexia, nausea and vomiting. Partial response was achieved in 1 of the 17 patients (7%). Median overall survival was 7.3 months.
  
  
  CONCLUSIONS
  Gemcitabine administered at a rate of 10 mg/m(2)/min was tolerated up to 1500 mg/m(2), but 1200 mg/m(2) represented a more appropriate recommended dose in further studies owing to neutropenia in Japanese patients with advanced pancreatic cancer.
authors.affiliation: Division of Hepatobiliary and Pancreatic Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan. jfuruse@east.ncc.go.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Michitaka
authors.initials: M
authors.lastname: Nagase
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshino
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine