The challenge of deciding when to administer uridine triacetate was explored by the panel.
Dr. Schwartzberg: I assume uridine triacetate would work more effectively if given very early; otherwise we would see the same kind of downstream toxicity we see with methotrexate.
Dr. Campen: Exactly, but this is difficult, because traditionally 5-FU has a very short half-life, about 5 to 10 minutes. The challenge is to know what the levels will be after infusion and to draw 5-FU levels and get a rapid turnaround time on those levels. In many cases, plasma 5-FU levels generally are < 0 ìg/L more than 3 hours after cessation of 5-FU dosing.
Dr. Schwartzberg: Are plasma 5-FU levels reliable in this setting? I would think that the drug works intracellularly, so they would not guide you very well.
Dr. Campen: If you start a continuous infusion by pump and look at plasma 5-FU levels, you do get a very reliable measurement of your AUC. But, at the same time, once you stop the pump, you also lose that very quickly too.
Ms. Vogel: So you should give uridine triacetate within the first 24 hours. If you have missed that 24-hour window, is it too late?
Dr. Campen: That is the unknown. The goal is to administer uridine triacetate within the first 24 hours, but it can be given up to 96 hours after 5-FU overdose per protocol.