Importance of preclinical investigations of the integration of capecitabine into polychemotherapy regimens

The introduction of capecitabine into the treatment of solid tumors is an example of the successful translation of biological principles into drug development. Tumor cells overexpress thymidine phosphorylase, which is critically involved in the activation of capecitabine to its cytotoxic metabolites. For this reason, improved activity of the drug with respect to 5-FU is obtained, and this finding has been confirmed by the study by Cao et al. In conclusion, preclinical data may be useful in planning combined treatment by using most effective drugs, but the balance between treatment effectiveness and drug-induced toxicity in some cases is not predictable, even if in vivo studies are performed, and a possible aid could arise from pharmacology studies addressing pharmacogenetics and drug metabolism, among other issues.