Hui-Ching Wang, Pen-Yuan Chu
Head and neck squamous cell carcinoma (HNSCC) remains associated with high rates of locoregional recurrence and distant metastasis despite definitive treatment. Metronomic tegafur-uracil (UFUR), an oral fluoropyrimidine comprising tegafur and uracil, has emerged as a potential maintenance strategy because of its cytotoxic, immunomodulatory, and anti-angiogenic mechanisms mediated by 5-fluorouracil (5-FU) and gamma-hydroxybutyric acid (GHB). This narrative review summarizes current evidence on UFUR maintenance in both resectable and unresectable HNSCC. Most available evidence is derived from retrospective and observational studies using maintenance durations ranging from approximately 6 months to 2 years. A recent meta-analysis of six observational studies (n = 1373) reported pooled hazard ratios of 0.68 for progression-free survival and 0.54 for overall survival; however, trial sequential analysis supported sufficient evidence only for progression-free survival, whereas the overall-survival evidence remained inconclusive. Published cohorts suggest potential benefits in selected high-risk patients and a generally manageable toxicity profile, but their findings remain susceptible to selection bias, residual confounding, and immortal-time bias. Prospective randomized trials are needed to confirm clinical benefit and define optimal treatment duration, patient selection, and potential integration with contemporary immunotherapy.