title: A phase II study of high-dose 24 hour continuous infusion 5-FU and leucovorin and low-dose PALA for patients with advanced pancreatic adenocarcinoma: a Southwest Oncology Group Study.
abstract: OBJECTIVE
  The purpose of this phase II multi-institutional study was to define the efficacy and toxicity of infusional 5-FU in combination with PALA and leucovorin in patients with advanced pancreatic cancer.
  
  
  METHODS
  Patients were required to have histologically confirmed pancreatic cancer that was locally advanced, unresectable or disseminated. The treatment regimen consisted of weekly 5-FU 2600 mg/m(2) given concurrently with leucovorin at 500 mg/m(2). Both drugs were administered by 24-hour continuous infusion. PALA was administered 24 hours prior to the administration of 5-FU/LV at a dose of 250 mg/m(2) IV over 15 minutes weekly. Patients were continued on the assigned treatment regimen until progression of disease, unacceptable toxicity, or the patient declined further therapy.
  
  
  RESULTS
  This study accrued 30 patients. Four of these patients were ineligible. All 26 eligible patients were evaluated for toxicity. One patient had inadequate assessment of response and was considered a non-responder. Three of the twenty-six eligible patients had partial responses, for a response rate of 12% (95% confidence interval 2% to 30%). All 26 eligible patients have died and the median overall survival was 7 months (95% confidence interval: 5.2 to 9 months). Four patients experienced grade 4 toxicities, including bilirubin increase (2 patients), vomiting (1 patient) and non-local skin ulceration (1). Two patients discontinued therapy due to toxicity.
  
  
  CONCLUSIONS
  The dual modulation of 5-FU with PALA and leucovorin in the dose and schedule used here, has a response rate similar to other single agents in pancreatic cancer and can result in some long term survival while having relatively mild toxicity.
authors.affiliation: University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Whitehead
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Benedetti
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Bach
authors.initials: B
authors.lastname: Ardalan
authors.forename: J Wendall
authors.initials: JW
authors.lastname: Goodwin
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Balcerzak
authors.forename: Wolfram E
authors.initials: WE
authors.lastname: Samlowski
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010865:Pilot Projects; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D002955:Leucovorin; D005472:Fluorouracil