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Capecitabine – a Novel Oral Tumor-Activated Fluoropyrimidine

The oral tumor-activated anticancer agent capecitabine is the first representative of a new class of cytostatics, the fluoropyrimidine carbamates. Capecitabine exploits the higher activity of the enzyme thymidine phosphorylase in malignant tissue compared to normal tissue to convert preferentially intra-tumoral capecitabine to 5-FU. In human cancer xenograft models, capecitabine treatment resulted in an highly improved efficacy compared to 5-FU and proved even to be effective in 5-FU-resistant cell lines. In clinical trials more than 1,400 patients have been treated so far with capecitabine. This drug has shown considerable antitumor activity. Objective response rates of 21–24% in metastatic colorectal cancer and 20% in heavily pretreated paclitaxel-resistant breast cancer patients were achieved. The side effects were predictable and well manageable, predominantly hand-and-foot-syndrome and diarrhea. Myelosuppression grade 3/4 was evident in less than 5%.Currently, several capecitabine phase II and III studies in patients with colorectal, breast and gastric cancer are ongoing, to further confirm the promising effects of capecitabine treatment.