New Directions With Capecitabine Combinations in Advanced Breast Cancer

ABSTRACT: Capecitabine (Xeloda) offers a unique mode of action. The drug is currentlybeing combined with other active agents in the treatment of advanced breastcancer. The recent demonstration of improved disease-free and overall survivalwith the capecitabine/docetaxel (Taxotere) combination, for example, hasencouraged investigation of additional capecitabine/taxane regimens andschedules. A unique aspect of the metabolic activation of capecitabine is theability of several anticancer drugs to upregulate the critical activating enzymethymidine phosphorylase. These preclinical findings have led to clinical trialsof several active agents in combination with capecitabine demonstrating highresponse rates in early results. In combination studies, capecitabine has beenassociated with very manageable toxicity. The combination of docetaxel/epirubicin(Ellence)/capecitabine (TEX) has shown particular promise in advanced disease,and should be evaluated in earlier disease. TEX is currently in phase III trialsof advanced disease. In preclinical studies, the combination of capecitabinewith inhibitors of HER2/neu (or the epidermal growth factor pathway) appears tohold significant promise both in breast cancer treatment and in treatment ofother tumors expressing these receptors. Continued evaluation of capecitabinecombinations will help to define the roles of this valuable agent, the only oralfluoropyrimidine for treatment of breast cancer available in the United States.[ONCOLOGY 16(Suppl 12):23-28, 2002]

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