In preclinical models, a synergistic interaction between capecitabine and docetaxel has been documented. One possible explanation for the synergy is that docetaxel up-regulates tumor levels of thymidine phosphorylase, the enzyme essential for the activation of capecitabine and 5'-dFUrd to 5-fluorouracil. Clinically, O'Shaughnessy, et al. recently reported improved survival with docetaxel/capecitabine combination therapy in patients with metastatic breast cancer, who previously failed anthracycline-containing chemotherapy. In this phase III study, patients were stratified according to previous exposure to paclitaxel and then randomized to capecitabine (Xeloda®) (1250 mg/m2 twice daily, days 1-14) plus docetaxel (75 mg/m2 day 1, repeated every 21 days) versus docetaxel alone. Grade 3 and 4 toxicities were more common in the docetaxel/capecitabine combination arm. Capecitabine (Xeloda®) and docetaxel were interrupted and the dosages reduced by 25% in patients who experienced a second occurrence of a given grade 2 toxicity, or any grade 3 toxicity, suggesting that the starting dosages were perhaps too high.