Oral Capecitabine vs Intravenous 5-FU in Colorectal Cancer: A Narrative Review

Background: Colorectal cancer [CRC] is the third most commonly diagnosed cancer and the second most common cause of cancer-related mortality worldwide. 5-fluorouracil [5-FU], administered intravenously, has traditionally been the reference fluoropyrimidine, although the oral prodrug capecitabine is activated by thymidine phosphorylase in tumors. Capecitabine often allows for more convenient administration, eliminates the need for a catheter, and has greater tumor specificity because of the enzymatic conversion to 5-FU.Objective: The purpose of this paper is to critically analyze and compare at a clinical level the efficacy, safety, pharmacokinetics, mechanism of action, toxicity profiles, and practical considerations of oral capecitabine and intravenous 5-FU in the treatment of CRC, by referencing current trials, meta-analyses, and real-world studies.Methods: Studies examining the use of capecitabine and 5-FU published from 2015-2025 were reviewed including randomized studies, pooled studies and real-world studies.Results: Capecitabine demonstrated similar efficacy to 5-FU in adjuvant, metastatic and neoadjuvant scenarios. The IDEA trial showed that three months of CAPOX had similar efficacy to six months for patients with low-risk stage III CRC, although oxaliplatin-induced neuropathy remains an issue. When capecitabine has been used in chemoradiotherapy, it achieved at least equal or better responses compared to 5-FU. Toxicities differed significantly between capecitabine and 5-FU. Capecitabine was more often associated with neutropenia, while 5-FU was more commonly associated with hand-foot syndrome and gastrointestinal- related events.Conclusion: Capecitabine is a highly efficacious and practical alternative to 5-FU for CRC treatment, and with further advances in pharmacogenetic targeting and combination regimens, gains will continue to be realized in clinical outcomes.