title: Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer.
abstract: BACKGROUND
  Advanced pancreatic cancer has limited treatment options. 5-fluorouracil (5-FU) is frequently used in the treatment of pancreatic cancer. Preclinical studies suggest synergism between trimetrexate (TMTX),5-FU, and leucovorin (NFL).
  
  
  OBJECTIVE
  We conducted a phase II trial to evaluate the activity and safety of NFL in pancreatic cancer.
  
  
  METHODS
  Eligible patients (n = 21) with untreated advanced pancreatic cancer were treated with 110 mg/m2 intravenous (IV) THTX on day 1 and 200 mg/m2 IV leucovorin prior to 500 mg/m2 IV 5-FU on day 2. Oral leucovorin (15 mg every 6 h for seven doses) started intravenous 24 h later.
  
  
  RESULTS
  Treatment was administered for 6 wk followed by a 2-wk rest period. Response was evaluated every 8 wk. All patients were evaluable for response and toxicity. Most patients (80%) had distant metastases. Forty-five cycles of chemotherapy were administered. The most common serious toxicities were Grade 3 diarrhea (23.8%) and nausea and vomiting (14.2%). The response rate was 4.1% (95% CI, 0-23%), median survival was 6.8 mo, and 1-yr survival was 19%.
  
  
  CONCLUSIONS
  Treatment with NFL is well-tolerated in patients with advanced pancreatic cancer. The median survival and 1-yr survival in these patients with poor prognosis compares favorably with other treatment options.
authors.affiliation: University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA. Agustin.Garcia@cshs.org
authors.forename: Agustin A
authors.initials: AA
authors.lastname: Garcia
authors.forename: Lawrence
authors.initials: L
authors.lastname: Leichman
authors.forename: Joaquina
authors.initials: J
authors.lastname: Baranda
authors.forename: Lalita
authors.initials: L
authors.lastname: Pandit
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Leichman
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D016597:Trimetrexate / Q000008:administration & dosage; D014839:Vomiting / Q000139:chemically induced
chemical_list: D002955:Leucovorin; D005472:Fluorouracil; D016597:Trimetrexate