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Rational Design of New Tumoractivated[sup TM] Cytotoxic Agents.
- Source :
-
Oncology . 1999 Supplement 1, Vol. 57, p9-15. 7p. - Publication Year :
- 1999
-
Abstract
- 5-Fluorouracil (5-FU) plays an important role in the treatment of several tumor types, particularly colorectal cancer and breast cancer. Xeloda[sup ®] (capecitabine; 5′-deoxy-5-fluoro-N-[(pentyloxy)carbonyl-cytidine]) is a new rationally designed fluoropyrimidine carbamate. It is administrated orally and after absorption it is first metabolized to 5′-deoxy-5-fluorocytidine (5′-DFCR) by carboxylesterase from the liver and then converted to 5′-deoxy-5-fluorouridine (5′-DFUR) by cytidine deaminase from the liver and tumor tissues. Finally, thymidine phosphorylase (TP) converts 5′-DFUR to 5-FU. TP is more active in tumor tissues than in normal tissue. This tissue localization pattern results in preferential metabolism and generates higher levels of 5-FU in malignant tissue, thus enhancing efficacy but minimizing side effects. The tumor tissue selectivity was confirmed in a study of 19 patients with colorectal cancer. After Xeloda administration, concentrations of 5-FU were 2.5 times higher in the primary tumor compared with adjacent healthy tissue. Xeloda was highly active in human tumor xenografts. It was more active than 5-FU, 5′-DFUR and tegafur plus uracil (UFT) and had a better therapeutic index. Xeloda also demonstrated synergistic or additive activity when used in combination with cyclophosphamide, methotrexate, doxorubicin, paclitaxel and docetaxel. This may be in part a result of up-regulation of TP by the cytotoxic agents. Phase I and II clinical trials have shown that Xeloda is active across a range of tumor types, and phase III studies are ongoing. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00302414
- Volume :
- 57
- Database :
- Academic Search Index
- Journal :
- Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 11380401
- Full Text :
- https://doi.org/10.1159/000055263