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The evolution of fluoropyrimidine therapy: from intravenous to oral Hoff PM; Cassidy J; Schmoll HJOncologist 2001[]; 6 Suppl 4 (ä): 3-11Chemotherapy for advanced colorectal cancer is based on i.v. 5-fluorouracil (5-FU). Numerous attempts have been made to increase the therapeutic benefit of 5-FU through schedule modification and biomodulation, but only modest improvements have been achieved. Capecitabine is an oral fluoropyrimidine that was developed in response to the clinical need for new therapeutic options offering improved efficacy, tolerability, and convenience for patients. Capecitabine was rationally designed to mimic continuous infusion 5-FU. It is rapidly and almost completely absorbed through the gastrointestinal wall and is converted to 5-FU via a three-step enzymatic cascade. 5-FU is generated preferentially in tumor by exploiting the higher activity of thymidine phosphorylase in tumor tissue compared with normal tissue. Results of a randomized, phase II trial led to the selection of a regimen of capecitabine for further clinical development (1,250 mg/m(2) twice daily for 14 days followed by a 7-day rest period). Subsequently, two large, randomized, phase III trials were conducted to compare capecitabine with i.v. bolus 5-FU/leucovorin ([LV]; Mayo Clinic regimen) in patients with metastatic colorectal cancer. A prospective, integrated analysis of data from the studies showed that capecitabine offers superior activity and an improved safety profile compared with 5-FU/LV. This article summarizes these developments in the treatment of colorectal cancer and assesses the feasibility of replacing i.v. 5-FU-based therapy with oral capecitabine. In addition, retrospective analyses assessing the impact of the dose modification scheme on the efficacy and tolerability of capecitabine are presented, and dose recommendations in special populations are reviewed.|Administration, Oral[MESH]|Antimetabolites, Antineoplastic/*administration & dosage/pharmacokinetics[MESH]|Capecitabine[MESH]|Clinical Trials as Topic[MESH]|Colorectal Neoplasms/*drug therapy/pathology[MESH]|Deoxycytidine/*administration & dosage/*analogs & derivatives/pharmacokinetics[MESH]|Drug Administration Schedule[MESH]|Fluorouracil/*administration & dosage/pharmacokinetics[MESH]|Humans[MESH]|Infusions, Intravenous[MESH]|Neoplasm Staging[MESH]|Randomized Controlled Trials as Topic[MESH]|Retrospective Studies[MESH] |
