title: A phase i study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel (FLTAX) as first-line therapy for advanced gastric cancer.
abstract: OBJECTIVE
  To determine the dose-limiting toxicity (DLT) and the maximum-tolerated dose (MTD) of combination chemotherapy with leucovorin-modulated weekly bolus 5-fluorouracil (5-FU) and weekly paclitaxel in patients with advanced gastric cancer (GC).
  
  
  METHODS
  Chemotherapy-naive patients with histologically proven metastatic or recurrent GC were enrolled. Paclitaxel was administered as a 1-h intravenous (i.v.) infusion followed by 5-FU as a bolus i.v. infusion on Days 1, 8 and 15. A 2-h i.v. infusion of l-leucovorin was started at the same time as the paclitaxel infusion on Days 1, 8 and 15. Treatment cycles were repeated every 28 days until disease progression or unacceptable toxicity occurred. Patients were scheduled to receive 5-FU, l-leucovorin and paclitaxel at four dose levels (mg/m(2)/week): 500/250/60 (level 1), 500/250/80 (level 2), 600/250/80 (level 3) and 600/250/100 (level 4), respectively.
  
  
  RESULTS
  Eighteen patients were enrolled. During the first cycle of the highest dose level (level 4), two of the six patients had DLT involving Grade 3 diarrhea and Grade 3 skin rash. Furthermore, three of the four patients who received the second consecutive cycle of treatment at dose level 4 had Grade 4 neutropenia. Dose level 3 was thus determined to be the MTD. Eleven (61%) of the 18 patients had partial responses, and the median progression-free survival time was 6.8 months.
  
  
  CONCLUSIONS
  The MTD and the recommended dose for phase II studies of this regimen were determined to be 5-FU 600 mg/m(2)/week, l-leucovorin 250 mg/m(2)/week and paclitaxel 80 mg/m(2)/week.
authors.affiliation: Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan. junjun0808@hotmail.com
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hirashima
authors.forename: Natsuko T
authors.initials: NT
authors.lastname: Okita
authors.forename: Takako E
authors.initials: TE
authors.lastname: Nakajima
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil