Capecitabine plus docetaxel combination chemotherapy for metastatic breast cancer

Doxifluridine(5'-DFUR)is converted to its metabolite 5-FU by the enzyme thymidine phosphorylase(TP). TP is expressed significantly higher in tumor tissue than in normal tissue. Capecitabine(N4-pentoxylcarbonyl -5'-deoxy-5-fluorocytidine)is a pro-drug of 5'-DFUR and a novel fluoropyrimidine carbamate that is converted to 5-FU preferentially in tumor tissue through a three-step enzymatic cascade. Expression of TP in tumor tissue may clinically predict efficacy of capecitabine. Induction of TP activity has brought about enhancement of capecitabine efficacy by taxanes in human cancer xenografts. In addition, a phase III study directly comparison docetaxel monotherapy and docetaxel plus capecitabine has been conducted for metastatic breast cancer patients who had received anthracyclines. The overall response rate of the combination group was 42%(n=255), and that of the monotherapy group was 30%(n=256)(p=0.006). The primary endpoints were time to disease progression, and time to treatment failure, and these parameters were superior in the combination arm than in the single arm, suggesting that capecitabine sensitization by docetaxel might be a new approach to breast cancer treatment.