Vision of the future: capecitabine

Capecitabine is a thymidine phosphorylase (TP)-activated oral fluoropyrimidine, rationally designed to generate 5-fluorouracil (5-FU) preferentially within tumors. This tumor selectivity is achieved through exploitation of the significantly higher activity of TP in tumor compared with healthy tissue. The high single-agent activity of capecitabine in breast and colorectal cancer suggests that capecitabine may have a role in the treatment of other tumor types that are sensitive to 5-FU, such as pancreatic cancer. Tumor types known to have a high level of TP activity, such as renal cancer, are especially attractive targets for capecitabine therapy. Capecitabine has potential as monotherapy in these tumor types, or as a combination partner for other cytotoxic agents with different mechanisms of action and little overlap of key toxicities. In particular, some cytotoxic drugs, such as the taxanes and cyclophosphamide, are known to upregulate TP activity in tumor tissue, offering the potential for synergistic action. The combination of capecitabine and docetaxel has demonstrated significant activity in women with anthracycline-pretreated breast cancer, and is the only cytotoxic combination to significantly increase survival compared with standard therapy in this setting. In addition, capecitabine as monotherapy or in combination with other cytotoxic agents has shown encouraging activity in pancreatic, ovarian, and renal cell cancers. This article discusses recent data from clinical trials investigating capecitabine in a range of tumor types, highlighting the potential future role of capecitabine as an alternative to traditional i.v. chemotherapy.