The evolution of fluoropyrimidine therapy: From intravenous to oral

Hoff, P., Cassidy, J. and Schmoll, H. (2001) The evolution of fluoropyrimidine therapy: From intravenous to oral. Oncologist, 6(Suppl.), pp. 3-11. (doi: 10.1634/theoncologist.6-suppl_4-3)

Abstract

Chemotherapy 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 (1250 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 5FU/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.

• Item Type: Articles
• Additional Information: Meeting of the Symposium on TP Activation: Convenience Through Innovation, FRANFURT, GERMANY, MAR 16-17, 2001
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cassidy, Professor James
• Authors: Hoff, P., Cassidy, J., and Schmoll, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncologist
• ISSN: 1083-7159