title: Low-dose trimetrexate glucuronate and protracted 5-fluorouracil infusion in previously untreated patients with advanced pancreatic cancer.
abstract: BACKGROUND
  5-Fluorouracil (5-FU)-based regimens have not been shown to prolong survival or provide clinical benefit in patients with advanced pancreatic cancer. The purpose of this study was to determine the tolerability of protracted venous infusion (PVI) of 5-FU, modulated by a low dose of the synthetic antifolate trimetrexate, in patients with advanced pancreatic cancer.
  
  
  METHODS
  Twenty-three chemotherapy-naïve patients were evaluated. Patients were enrolled in four consecutive cohorts in which the weekly dose of trimetrexate was escalated in 10 mg/m2 increments, from 20 to 50 mg/m2. PVI 5-FU was administered at a fixed dose of 225 mg/m2/day. Treatment was administered for 6 successive weeks, every 8 weeks.
  
  
  RESULTS
  Twenty-two patients were assessable. The maximum tolerated dose of trimetrexate was 40 mg/m2. The most common grade 3 and 4 toxicity was diarrhea. There were no treatment-related deaths. Preliminary analysis of activity revealed a response rate of 9%, with 41% of the patients having stable disease for a median duration of 3.8 months. The median survival for the entire group was 6.9 months (range 1-29 months). A clinical benefit response was experienced by 27.2% of patients.
  
  
  CONCLUSIONS
  Low-dose trimetrexate can be safely administered in combination with PVI 5-FU. This treatment is well tolerated and is associated with palliative activity in advanced pancreatic cancer.
authors.affiliation: Division of Hematology/Oncology and Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095-1678, USA. ramado@ucla.edu
authors.forename: R G
authors.initials: RG
authors.lastname: Amado
authors.forename: L S
authors.initials: LS
authors.lastname: Rosen
authors.forename: J R
authors.initials: JR
authors.lastname: Hecht
authors.forename: L S
authors.initials: LS
authors.lastname: Lin
authors.forename: P J
authors.initials: PJ
authors.lastname: Rosen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005965:Glucuronates / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016597:Trimetrexate / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D005965:Glucuronates; C056321:trimetrexate glucuronate; D005472:Fluorouracil; D016597:Trimetrexate