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

Abstract

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 metastatic breast 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 was excluded on grounds of quality.

Data Summary. 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. The 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 including breast cancers, resulting in preferential delivery of 5-FU to tumour tissues, and suggesting a greater potential for selective cytotoxicity than is seen with 5-FU.

Capecitabine has been examined both alone and in combination with a variety of cytotoxic drugs in the treatment of metastatic breast cancer. To date, clinical evidence supports the use of capecitabine monotherapy in patients relapsing after prior treatment with anthracyclines and taxanes and in combination with docetaxel in patients failing anthracycline treatment.

Data from phase II studies indicate that in the first of these situations, capecitabine elicits a response in about one-fifth of patients and that responses are associated with symptomatic relief and extended survival. In the latter situation, a phase III study has shown that the combination of docetaxel and capecitabine elicits superior response rates, remission durations, and overall survival compared with the taxane alone and with no clinically important increase in toxicity.

Used alone or in combination, the most notable adverse effect associated with capecitabine is palmar-plantar erythrodysasthesia (hand -foot syndrome), a characteristic complex of reddening, dryness, and soreness of the palms of the hands and soles of the feet, which is rarely disabling and readily managed by treatment interruption and dose reduction.