The significant effect that scheduling has upon the severity and
types of drug toxicity has been known for many years. Evidence is available
demonstrating that the schedule chosen will substantially effect the relative
distribution of drug to various target organs. It has been shown that a likely
cause for this with doxorubicin is that the efficiency of the various enzyme
complexes responsible for disposing of the drug can be affected by scheduling.
We believe a similar process can explain the marked effect that scheduling has
on the pattern of 5-fluorouracil toxicity and present both clinical and
computer data to illustrate this.