 There is a theoretical advantage to using paclitaxel on a weekly schedule in conjunction with capecitabine based on the duration of the upregulation of thymidine phosphorylase dThPase by paclitaxel in model systems. The metabolism of capecitabine to the active agent, FU, provides insight into the rationale for combining capecitabine with taxanes in this phase II study . The rationale for combining paclitaxel with capecitabine is based on the upregulation of dTHPase, which has been demonstrated in a model of athymic mice bearing capecitabine-resistant human colon cancer xenografts. Treatment with paclitaxel led to a 7.9-fold increase in intratumoral dThPase. An increase in dThPase activity occurred 4 days after treatment with paclitaxel and persisted for 10 days . These data led to the current concept for this clinical trial, using paclitaxel on days 1 and 8 during a 14-day exposure to capecitabine in patients with MBC. Moreover, these agents have nonoverlapping toxicities and therefore can be combined with reasonable tolerability. It was anticipated that by allowing a week off from weekly paclitaxel therapy, the frequency of sensory neuropathy could be reduced. 