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

Invest New Drugs. 2004 Aug;22(3):335-41. doi: 10.1023/B:DRUG.0000026261.76197.54.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aspartic Acid / administration & dosage
  • Aspartic Acid / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Infusions, Intravenous
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Phosphonoacetic Acid / administration & dosage
  • Phosphonoacetic Acid / analogs & derivatives*
  • Pilot Projects
  • Prospective Studies
  • Survival Rate
  • Treatment Outcome

Substances

  • Aspartic Acid
  • sparfosic acid
  • Phosphonoacetic Acid
  • Leucovorin
  • Fluorouracil