The applicant proposes to study IP biochemical modulation of FUdR given with IP leucovorin and to determine its pharmacologic and clinical consequences. Fluoropyrimidine catabolic pathways as well as changes in the customary pharmacologic parameters will be measured. In addition, he will attempt to establish the pharmacodynamic effects of such modulation, and to evaluate portal versus systemic FUdR levels in selected patients. Such studies may impact on development of adjuvant therapies. Finally, an animal model will assist in studying pharmacologic consequences of IP FUdR + leucovorin further, and allow study of other forms of biochemical modulation or other modalities in combination.
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