Clinical development of new fluoropyrimidines: a major improvement in colorectal cancer treatment?

Aims And Background: Colorectal cancer represents an increasing problem and is responsible for about 16,000 deaths per year in Italy. Fluorouracil represents the most widely used agent, but therapeutic responses have remained consistently discouraging. The overall response rates for fluorouracil as a single agent range from 5% to 15%, and the addition of biochemical modulators, although able to improve response rate, has not been shown conclusively to prolong survival.

Methods: In recent years, several new compounds characterized by a high therapeutic index, optimal absorption through the gastrointestinal tract when administered orally and selective hepatic metabolization have been synthesised. In this review we analyzed published data on new fluoropyrimidines in an attempt to better define their role and to evaluate any significant improvement over fluorouracil.

Results: Although no sure advantage over fluorouracil has been detected, interesting results have been reported for fluorouracil analogs with alternative routes of administration such as oral or intra-arterial chemotherapy.

Conclusions: Further studies, possibly randomized, should also measure quality of life and treatment-related costs in order to define their real advantage over fluorouracil in the palliation of advanced colorectal cancer.