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Capecitabine: a novel, orally administered, tumour-activated treatment for colorectal cancer

The Pharmacy Department, Guy’s Hospital, St. Thomas’ Street, London SE1 9RT, UK

Objective. To provide a comprehensive review of the preclinical and clinical pharmacology and toxicology of the fluoropyrimidine, capecitabine, with particular reference to its use in its new indication, advanced colorectal cancer.

Data sources. A MEDLINE search was conducted using the term ‘‘capecitabine’’ for the period 1995 -2001. The reference lists from retrieved articles were reviewed and other relevant papers identified. The abstract books from the annual meetings of the American Society of Clinical and Oncology and the European Society of Medical Oncology were also reviewed.

Data extraction. The aim of the review was to be comprehensive and descriptive. All studies containing information deemed to be of interest were reviewed by the author, none were excluded on grounds of quality.

Data synthesis. Capecitabine is a prodrug of the widely used cytotoxic agent 5-fluorouracil (5-FU). Unlike 5-FU it is extensively and reliably absorbed after oral administration and does not require folinate (FA) potentiation. Activation of capecitabine is a three-step enzymatic process. The final activating enzyme, thymidine phosphorylase, is found in unusually high concentrations in many solid tumours, resulting in preferential delivery of 5-FU to tumour tissues, including that of colorectal cancers, suggesting therapeutic potential in this malignancy. Large, randomized trials have demonstrated that capecitabine fulfils this potential—compared with the widely used ‘‘Mayo’’ regimen of intravenous 5-FU and folinic acid, oral capecitabine (1250 mg/m² twice daily) produced a superior response rate and a similar time to disease progression and duration of survival. It was also better tolerated than 5-FU/FA—of seven common fluoropyrimidine-induced toxicities, four were significantly less common with capecitabine. Capecitabine also produced significantly less grade 4 toxicity or toxicity requiring hospitalization, though the hand -foot syndrome that characterizes prolonged, continuous exposure to 5-FU was more common after capecitabine.

Key Words: capecitabine • chemotherapy • colorectal cancer • fluoropyrimidines

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