Capecitabine and docetaxel in the treatment of metastatic breast cancer: combination, sequence or single agent?

Capecitabine is preferentially activated to 5-fluorouracil in tumour tissue by thymidine phosphorylase (TP). When combined with agents known to upregulate TP, such as docetaxel, a synergistic interaction was noted in preclinical models. In a phase III clinical trial, the combination of capecitabine plus docetaxel yielded improved response rates, progression-free survival and an absolute survival benefit of 3 months compared with docetaxel alone. Combination therapy was associated with significantly more diarrhoea, stomatitis, hand-foot syndrome and nausea and vomiting, although dose reductions can reduce these side-effects while maintaining a survival benefit. The superiority of the combination as opposed to the sequential use of these drugs remains unclear. There is interest in developing single-agent capecitabine as first-line treatment for patients with more indolent disease where, as a consequence of improved tolerability, continued use may lead to improvements in overall survival.