Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a Southwest Oncology Group study.

Abstract

From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.

• Authors: James H Doroshow, Sheryl McCoy, John S Macdonald, Brian F Issell, Taral Patel, Patrick W Cobb, Kathleen J Yost, James L Abbruzzese
• Journal: Investigational new drugs (Invest New Drugs) Vol. 24 Issue 6 Pg. 537-42 (Nov 2006) ISSN: 0167-6997 [Print] United States
• PMID: 16832602 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acetates
• uridine triacetate
• Leucovorin
• Fluorouracil
• Uridine

Topics

• Acetates
• Adenocarcinoma (drug therapy, mortality, secondary)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage)
• Humans
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Stomach Neoplasms (drug therapy, mortality, pathology)
• Survival Analysis
• Uridine (administration & dosage, analogs & derivatives)