Spotlight on Capecitabine in Colorectal Cancer

Abstract

Capecitabine is an orally administered fluoropyrimidine which is selectively activated in tumor tissue to the active moiety fluorouracil and is cytotoxic through inhibition of DNA synthesis.

In patients with advanced or metastatic colorectal cancer, first-line therapy with intermittent capecitabine achieved significantly higher objective tumor response rates than therapy with fluorouracil plus leucovorin in pooled analysis. Response rates were also higher in patients pretreated in the adjuvant setting and whose primary site of metastasis was the lung. However, no significant differences between the two treatment groups were seen in the time to disease progression, time to treatment failure or overall survival.

Preliminary data suggest that response may be improved by combining capecitabine with other anticancer therapies such as oxaliplatin, irinotecan and radiotherapy.

Capecitabine in therapeutic dosage regimens generally has acceptable tolerability. Diarrhea and hand-and-foot syndrome are the major dose-limiting toxicities associated with capecitabine therapy, with adverse effects generally of a gastrointestinal nature. Overall, diarrhea, stomatitis, nausea and alopecia were significantly less common with capecitabine than with bolus fluorouracil and leucovorin. In addition, capecitabine recipients experienced significantly less myelosuppression, although more capecitabine recipients discontinued therapy because of adverse events. Importantly, patients spent less time in hospital after capecitabine than after bolus fluorouracil and leucovorin therapy, and the oral route of administration of capecitabine is likely to be preferred.

In conclusion, capecitabine has shown superior tumor response, less myelosuppression, but more grade 3 hand-and-foot syndrome, in comparison with the ‘Mayo Clinic’ regimen of fluorouracil therapy, but is unlikely to improve survival. Significantly, its oral route of administration is likely to be preferred by patients. Future strategies to improve patient response may involve selection of those patients likely to respond best to capecitabine, through determination of relevant enzyme levels and combination of capecitabine with various antineoplastic agents. Data on the effect of the drug on quality of life would help to further establish its role. In the meantime, capecitabine appears to offer an effective and more convenient alternative to fluorouracil as first-line monotherapy for the treatment of metastatic colorectal cancer.