Daryl S. Sonnichsen, PharmD

Therapeutic options for patients with advanced colorectal cancer who have failed treatment with fluorouracil (5-FU) are limited. Responses have been reported in this setting with a protracted venous infusion of 5-FU. Daily oral therapy with tegafur and uracil (UFT) plus leucovorin (LV) has the potential to mimic the pharmacology of continuous infusion 5-FU. Therefore, we undertook a phase II study of a 28-day schedule of a combination chemotherapy regimen containing oral UFT/leucovorin in patients with measurable metastatic colorectal cancer who had failed treatment with bolus 5-FU. In addition, we sought to determine whether coadministration of UFT and leucovorin alters the bioavailability of these agents. In a pretreatment phase, each patient underwent sequential pharmacokinetic sampling following a single dose of UFT alone, leucovorin alone, and the combination of UFT plus leucovorin. The preliminary results of this trial suggest that tegafur pharmacokinetics are not affected by coadministration of leucovorin and that folate pharmacokinetics are not affected by UFT. [ONCOLOGY 11(Suppl 10):22-25, 1997]