Capecitabine versus 5-fluorouracil in colorectal cancer: where are we now?
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REVIEW
Capecitabine versus 5-fluorouracil in colorectal cancer: where are we now? Lakshmi Chintala • Susmitha Vaka • Joaquina Baranda • Stephen K. Williamson
Received: 19 November 2010 / Accepted: 2 March 2011 / Published online: 9 April 2011 Ó The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract Fluorouracil (5-FU) remains the most widely used agent for colorectal cancer. Capecitabine is a rationally designed 5-FU pro-drug developed to mimic the continuous infusion of 5-FU while avoiding complications and inconvenience of intravenous administration. Capecitabine is absorbed intact from the gastrointestinal tract, converted enzymatically to active 5-FU, and released directly into the tumor. Capecitabine’s efficacy and safety are shown in multiple phase III trials across different disease stages and therapy lines. Three randomized phase III trials demonstrated the equivalence of capecitabine plus oxaliplatin (XELOX) versus 5-FU/leucovorin (LV)/oxaliplatin (FOLFOX). The safety of capecitabine compared with 5-FU depends on the regimen of 5-FU used. The adverse event rate with oxaliplatin in combination with infusional 5-FU is similar to that of capecitabine plus oxaliplatin but is associated with more neutropenia and venous thrombotic events; capecitabine plus oxaliplatinbased regimens tend to be associated with more grade 3 diarrhea and hand-foot skin reaction. Combination therapy with capecitabine and irinotecan (CapeIRI) versus 5-FU/ LV and irinotecan (FOLFIRI) had more variable results; some former schedules resulted in excessive treatmentrelated toxicity. More recent data show that lower capecitabine and irinotecan doses, different schedules, and combination with targeted agents (e.g, bevacizumab) have resulted in more favorable outcomes.
L. Chintala S. Vaka J. Baranda S. K. Williamson (&) Division of Hematology/Oncology, University of Kansas Cancer Center, 2330 Shawnee Mission Parkway, Suite 210, Westwood, KS 66205, USA e-mail: [email protected]
Keywords Capecitabine Chemotherapy Colorectal cancer Combination therapy Fluorouracil
Introduction The most widely used agent in the treatment of colorectal cancer (CRC) is fluorouracil (5-FU), which was developed more than 50 years ago by Heidelberger et al. [1]. 5-FU enters a complex anabolic process that interferes with normal DNA and RNA functions and accounts for cytotoxicity at the cellular level. Because of poor oral absorption and intra-patient variability, 5-FU is most often administered intravenously (IV) as a rapid bolus injection; it is rapidly distributed, with triphasic elimination [2]. Preclinical studies suggested that 5-FU is a time-dependent drug, and that cytotoxicity increases with prolonged exposure [2–4]. Therefore, clinical trials were initiated with 5-FU administered for extended periods [5, 6]. Response rates in CRC increased with continuous infusion compared with bolus administration, with a more acceptable toxicity profile [7, 8]. Nevertheless, the inconvenience of protracted IV administr
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