Medline ® Abstracts for References 146-149
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
Uridine allows dose escalation of 5-fluorouracil when given with N-phosphonacetyl-L-aspartate, methotrexate, and leucovorin.
Seiter K, Kemeny N, Martin D, Schneider A, Williams L, Colofiore J, Sawyer R
Cancer. 1993 Mar;71(5):1875-81.
BACKGROUND: In a previous trial in which methotrexate and N-phosphonacetyl-L-aspartate (PALA) were used to modulate 5-fluorouracil (5-FU), four of six patients could not tolerate treatment at the 600 mg/m2 5-FU dose level because of mucositis, diarrhea, and a decrease in performance status. The current study examines the ability of uridine rescue to prevent such toxic effects in the same regimen and, thereby, allow additional dose escalation of 5-FU.
METHODS: Twenty-nine patients with advanced malignant neoplasms received PALA and MTX, each at 250 mg/m2, followed 24 hours later by increasing bolus doses of 5-FU (600-750 mg/m2) with a leucovorin rescue (10 mg orally every 6 hours for eight doses) and uridine rescue (3 g/m2/hour, for a 72-hour infusion, 3 hours on, 3 hours off). Treatment was repeated weekly with either 2 weeks on, 2 weeks off, or 3 weeks on, 1 week off.
RESULTS: Mucositis, which occurred in 4 of 12 patients treated at the 750 mg/m2 5-FU dose level, was the only significant chemotherapy-induced toxic effect. However, uridine-related central venous catheter complications (cellulitis in six patients and superior vena cava syndrome in one patient) precluded additional treatment on this protocol.
CONCLUSIONS: In the current regimen, uridine allowed dose escalation of 5-FU to 750 mg/m2, which some patients tolerated on a 3-week on, 1-week off schedule. Because of the vascular toxic effects associated with intravenous uridine, the authors recommend additional studies with oral uridine to determine whether the increase in 5-FU dose that uridine allows is associated with improved response rates.
Gastrointestinal Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Enhancement of the antitumor activity of 5-fluorouracil by uridine rescue.
Klubes P, Leyland-Jones B
Pharmacol Ther. 1989;41(1-2):289-302.
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Saif MW, Borstel RV. PN401 rescue from the lethal toxicity of 5-FU in mice (abstr 3737). In: Proceedings of American Association for Cancer Research, University of Chicago Press, Chicago 2003. Vol 44, p.744.
no abstract available
Vistonuridine: An orally administered, life-saving antidote for 5-fluorouracil (5FU) overdose.
von Borstel R, O'Neil J, Bamat M
J Clin Oncol. 2009;27(15s):abstr 9616.