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7563807 
Journal Article 
The prevention of breast cancer: Is genetics just diversionary? 
Pike, M; , 
2002 
Yes 
European Journal of Cancer
ISSN: 0959-8049
EISSN: 1879-0852 
38 
SUPPL. 2 
S3 
English 
Capecitabine is a fluoropyrimidine carbamate that was rationally designed as an oral drug capable of mimicking continuous infusion 5-fluorouracil (5-FU) and delivering 5-FU preferentially to tumour tissue. Following extensive absorption, capecitabine is rapidly converted to 5-FU via a three-step enzymatic pathway. The final step depends on thymidine phosphorylase, an enzyme present at higher concentrations in malignant compared with normal tissue. This results in the delivery of 5-FU preferentially to the tumour site. Capecitabine has demonstrated high activity in preclinical xenograft models for a wide range of human solid tumours, including those resistant to 5-FU. Phase I studies have determined the maximum tolerated dose (MTD) of capecitabine and identified a number of dosage regimens, which were subsequently evaluated in a randomised, phase II study as first-line treatment for metastatic colorectal cancer. This established an intermittent regimen of capecitabine 1250 mg/m2 twice daily for 14 days followed by a 7-day rest period as the most appropriate regimen for further clinical development. © 2002 Published by Elsevier Science Ltd. 
Capecitabine; Fluoropyrimidine; Pharmacodynamics; Pharmacokinetics; Thymidine phosphorylase; 5' deoxy 5 fluorocytidine; capecitabine; cyclophosphamide; docetaxel; doxifluridine; drug metabolite; fluorouracil; folinic acid; mitomycin C; paclitaxel; thymidine phosphorylase; unclassified drug; antineoplastic activity; article; cancer chemotherapy; cancer inhibition; chemical modification; clinical trial; colorectal cancer; drug absorption; drug activation; drug activity; drug blood level; drug efficacy; drug half life; drug selectivity; enzyme mechanism; food drug interaction; human; maximum tolerated dose; priority journal; side effect; solid tumor; xenograft; Administration, Oral; Animals; Antimetabolites, Antineoplastic; Clinical Trials, Phase I; Clinical Trials, Phase II; Colorectal Neoplasms; Deoxycytidine; Humans; Mice; Mice, Nude; Prodrugs; Randomized Controlled Trials; Survival Analysis 
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