Circadian pattern of continuous FUDR infusion reduces toxicities

The toxicity and efficacy of at least a dozen of the most commonly used anticancer drugs vary predictably depending on when in the day they are given. In a series of murine experiments involving CD2F1 mice, we have demonstrated that the safest time for FUDR administration is the mid- to late activity span. In a clinical pilot study, an implantable programmable drug-administration device (Medtronic, Inc), allowing automatic dose modifications of continuous long-term infusion, was employed to investigate whether this is also true in cancer patients. Toxicity of FUDR given as continuous flat infusion was significantly greater than that of time-modified infusion regardless of the route of drug administration. Responses have occurred with at least equal frequency, and patients are currently being followed to see if the pattern of drug delivery has an effect on patient survival.