Drug Insight:: metastatic colorectal cancer -: oral fluoropyrimidines and new perspectives in the adjuvant setting

Capecitabine and uracil/ftorafur (UFT) are prodrugs of 5-fluorouracil (5-FU) that can be administered orally. Both drugs have been shown to be as effective as bolus 5-FU and folinic acid (FA), both as adjuvant treatment, and for the treatment of metastatic colorectal cancer. However, as the addition of oxaliplatin to 5-FU has been shown to improve disease-free survival in adjuvant therapy, oxaliplatin/5-FU is currently regarded as the standard adjuvant treatment, rather than fluoropyrimidine monotherapy. For the treatment of metastatic colorectal cancer, improved response rates and prolonged survival have been reported when irinotecan or oxaliplatin was added to 5-FU/FA; a further increase in efficacy was shown when bevacizumab, an antibody to vascular endothelial growth factor, was added to chemotherapy. Studies investigating the substitution of infusional 5-FU with oral compounds in combination therapy (e.g. FOLFOX versus capecitabine/oxaliplatin) are ongoing, but preliminary results in metastatic patients advise caution because of increased toxicity when used with irinotecan, and statistically non-significant trends of a decreased efficacy when used with oxaliplatin. Therefore, the combined use of oral 5-FU prodrugs plus irinotecan or oxaliplatin is not recommended at present. Oral 5-FU prodrugs, however, offer a convenient and less toxic treatment option in adjuvant treatment and in the treatment of advanced colorectal carcinoma in patients who do not want an intensified regimen, those that have contraindications for implanted venous access devices, and those who are not candidates for a combination therapy with irinotecan and oxaliplatin.