LAUSR

Opinion statementNowadays, systemic chemotherapy with intravenous (IV) 5-fluorouracil (5-FU) remains the most commonly prescribed treatment for metastatic colorectal cancers (CRC), in combination with other cytotoxic drugs. 5-FU can be administered through a bolus injection or continuous infusion (cIV), with the latter becoming the preferred administration method and standard of care in recent years. Oral fluoropyrimidines were developed to overcome challenges associated with the IV administration of 5-FU, among which capecitabine has become the most widely used one. However, although capecitabine and other oral fluoropyrimidine-based regimens are more convenient to administer, their efficacy and safety in comparison with IV 5-FU are not well understood. Results from recent randomized controlled trials, observational studies, and meta-analyses have been inconsistent. Safety, in particular, remains controversial. Our review, a first comprehensive meta-analysis comparing the efficacy and safety of cIV 5-FU with capecitabine, the two most widely used fluorouracil modalities in CRC, showed that cIV 5-FU-based regimens are associated with greater response rates compared with capecitabine-based regimens, with no difference in progression-free survival, time to treatment failure, overall survival, or disease-free survival between the two. Furthermore, cIV 5-FU-based regimens showed an improved safety profile compared with capecitabine-based regimens. Our findings suggest that cIV 5-FU remains a more effective and safer modality of fluorouracil administration than capecitabine, thus providing supporting evidence to guide clinical practice in the management of colorectal cancer.