Fluorinated pyrimidines in oral treatment of advanced colorectal cancer

For several years, fluorinated pyrimidines have been used in the treatment of advanced colorectal cancer, mainly in the form of intravenous injections of 5-fluorouracil (5-FU), alone or in combination with leucovorin. Oral treatment with 5-FU has been difficult because of high toxicity and low bioavailability. Increased knowledge of the metabolism of 5-FU, reviewed in this article, has led to the development of a number of new oral drugs for the treatment of advanced colorectal cancer. Administration of prodrugs and inhibitors of 5-FU-catabolic enzymes has led to stable and high levels of active drug. Several drugs have shown promising results in new clinical trials. New 5-FU related drugs for oral administration show results comparable to those of the cytotoxic drugs that have been administered in hospital. In the future, general practitioners could possibly treat and follow up a larger proportion of these patients.