Oral therapy for colorectal cancer: how to choose

Either alone or in combination with other antineoplastics, fluorouracil (5-FU) has been the mainstay of treatment of gastrointestinal, breast, and head and neck cancers for the past 40 years. Numerous active 5-FU schedules are in clinical use, but erratic oral bioavailability has historically mandated intravenous administration. Recently, two methods have been used to overcome the poor oral bioavailability of 5-FU. The first involves the use of prodrugs that are absorbed intact in the gastrointestinal tract and are ultimately converted to 5-FU in normal or tumor tissues. An alternate approach involves the inhibition of gastrointestinal degradation via coadministration of an inhibitor of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in 5-FU catabolism. The oral fluoropyrimidines currently in development result in prolonged exposure to 5-FU and, therefore, have the potential to achieve clinical benefits similar to those seen with protracted intravenous infusions of 5-FU, but without the cost, complications, and inconvenience of ambulatory infusion pumps. This review describes several oral fluoropyrimidine regimens with activity in colorectal cancer: capecitabine (Xeloda), tegafur, UFT, S-1, and eniluracil plus 5-FU. An understanding of the distinct mechanisms of action and toxicity patterns of each regimen may ultimately guide treatment selection when multiple choices become available.