Capecitabine: a novel agent for the treatment of solid tumors

Although 5-fluorouracil (5-FU) has been used to treat breast and colorectal cancers for several decades, bolus 5-FU has disappointing efficacy. Prolonged infusion schedules and biomodulation with leucovorin have resulted in improved response rates, but these have not translated into significant improvements in survival in patients with metastatic disease. Furthermore, prolonged infusion is inconvenient for patients and can result in medical complications. New oral fluoropyrimidines, including capecitabine, are promising alternatives to i.v. 5-FU. Capecitabine generates 5-FU preferentially within tumors through exploitation of the high intratumoral activity of thymidine phosphorylase. The tumor selectivity of capecitabine has been confirmed in a clinical study of colorectal cancer patients. Clinical trials have shown that capecitabine is an effective, well-tolerated treatment for breast and colorectal cancer, with response rates of 20-26% in anthracycline- and taxane-pretreated metastatic breast cancer. As first-line monotherapy, capecitabine produces response rates of 25-27% in metastatic colorectal cancer and 30% in metastatic breast cancer. In all studies to date, capecitabine has been well tolerated, with adverse events typical of infusional 5-FU and manageable with treatment interruption/dose modification. Myelosuppression and alopecia are rare. Capecitabine is also being investigated in other solid tumors (including ovarian, pancreatic and gastric cancers) as adjuvant monotherapy in breast and colorectal cancer, and in combination with other cytotoxic agents. Results of ongoing trials are eagerly awaited.