Practical considerations in the use of oral fluoropyrimidines.

Since its synthesis over 40 years ago, several studies including patients with colorectal cancer have shown that prolonged exposure to 5-fluorouracil (5-FU) is associated with better antitumor activity and decreased toxicity. However, the use of continuous-infusion 5-FU is costly and is associated with the need for a catheter and infusion pump. The use of an oral formulation of 5-FU allows protracted exposure without the inconvenience and cost of intravenous continuous-infusion regimens. Capecitabine is a rationally designed fluoropyrimidine that can be given orally and uses the high concentration of thymidine phosphorylase within cancer cells to concentrate heavily within the tumor. Two large randomized studies that included patients with metastatic colorectal cancer have shown superior response rates for capecitabine compared with bolus regimens of 5-FU with equal times to progression, overall survival, and duration of response. Because of its favorable toxicity profile and the efficacy shown in early trials, capecitabine is currently being investigated in the adjuvant setting and in combination with radiotherapy and with other chemotherapy agents.