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Oral Fluoropyrimidines: Are They the Equivalent of Parenteral Infusional 5-Fluorouracil?

The recent introduction of three oral fluoropyrimidine preparations to the antineoplastic armamentarium has been welcomed as a major step forward in providing a patient-convenient delivery system for 5-fluorouracil (5-FU) and is perceived as a potential means of replacing infusional parenteral delivery of 5-FU, which is a common treatment for a variety of tumor types including head and neck cancer, esophageal cancer, rectal cancer, and anal cancer. Variable and erratic bioavailability of the standard formulation of 5-FU in terms of absorption via the gastrointestinal tract precludes the oral route as a reliable means of delivery of the standard formulation of 5-FU in the clinic, but the three oral 5-FU preparations are characterized by excellent gastrointestinal absorption due to inhibition of intestinal dihydropyrimidine dehydrogenase (DPD, an enzyme critical to 5-FU catabolism) (by eniluracil and the uracil component of uracil, 5-FU, and tegafur [UFT]) or a DPD-independent agent which is a prodrug of 5-FU (capecitabine). Each of the agents is administered two or three times per day for 14 or 28 days, conceptionally emulating the continuous parenteral infusion of 5-FU. Each of the agents has been compared to 5-FU plus leucovorin in large randomized trials (1– 4), but only eniluracil plus 5-FU is being studied in a Phase III comparative trial against parenteral infusional