Oral Tegafur-Uracil Combination plus Leucovorin versus Other Fluoropyrimidine Agents in Colorectal Cancer: A Systematic Review and Meta-Analysis

Background Systemic fluoropyrimidines, both oral and intravenous, are an integral part of colorectal cancer (CRC) management. They can be administered either with curative or palliative intent. Objectives This article examines the literature to analyze the efficacy and safety of the oral fixed-dose combination of uracil and tegafur (UFT)/leucovorin (LV) compared with other fluoropyrimidine agents, with an intention to implement the findings into the current treatment algorithms for CRC. Methods An exhaustive systematic literature search was performed for prospective studies using PUBMED, Cochrane Library, and EMBASE database. Studies which met eligibility criteria were shortlisted and grouped into chemotherapy given for curative or palliative intent. Results Eight trials were shortlisted involving 4,486 patients for the analysis. There was no difference between UFT/LV and other fluoropyrimidines in the primary endpoints—disease-free survival (hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.90–.15; p = 0.81) and progression-free survival (HR 0.87; 95% CI 0.66–.66; p = 0.35) for curative and palliative intent CRC patients, respectively. In secondary analyses, there was no significant difference observed between UFT and other fluoropyrimidines in overall survival in CRC patients with curative intent (HR 1.04; 95% CI 0.88–1.23; p = 0.63) and palliative intent (HR 1.02; 95% CI 0.97–1.06; p = 0.42) . In the safety analysis, we found significantly lesser patients on UFT/LV had stomatitis/mucositis (odds ratio [OR] 0.20; 95% CI 0.05–0.85; p = 0.03), fever (OR 0.46; 95% CI 0.29–0.71; p < 0.001), infection (OR 0.42; 95% CI 0.24–0.74; p < 0.01), leukopenia (OR 0.04; 95% CI 0.00–0.95; p = 0.05), febrile neutropenia (OR 0.03; 95% CI 0.00–0.24; p = 0.001), and thrombocytopenia (OR 0.14; 95% CI 0.02–0.79; p = 0.03) compared with other fluoropyrimidines. Conclusion Oral UFT/LV is equally efficacious to other fluoropyrimidines, especially intravenous 5-fluorouracil, in the management of early as well as advanced CRC patients. Importantly, UFT/LV has a superior safety profile compared with other fluoropyrimidines in terms of both hematological and nonhematological adverse events.