Tegafur-Uracil Maintenance Therapy in Non-Metastatic Head and Neck Cancer: An Exploratory Systematic Review

Tegafur-uracil (UFT), an oral fluoropyrimidine developed in Asia, has been investigated as a maintenance or adjuvant therapy in various malignancies. Its use in head and neck cancers, however, remains limited to small retrospective studies, primarily from East Asia. Given the need for cost-effective maintenance strategies in resource-limited settings, we conducted an exploratory systematic review to evaluate the clinical utility of UFT in non-metastatic head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC).

We systematically searched PubMed, EMBASE, and Cochrane Library from inception through 1 May 2025 for retrospective cohort studies evaluating UFT after definitive therapy in non-metastatic HNSCC or NPC. Study selection followed PRISMA guidelines. Given the heterogeneity of included studies, we performed a structured narrative synthesis using the SWiM (Synthesis Without Meta-analysis) framework to summarize survival outcomes, treatment settings, and clinical contexts.

Seven retrospective studies (four HNSCC, three NPC) involving 508 patients were included. UFT was generally administered at 300-400 mg/day for 6-12 months. Across studies, UFT use was associated with favorable disease-free and overall survival trends in high-risk subgroups, including patients with extranodal extension and persistent EBV DNA. Treatment adherence and toxicity profiles were acceptable.

While the evidence remains limited and heterogeneous, this review highlights recurring signals of benefit associated with UFT maintenance therapy in selected high-risk patients. Prospective trials are warranted to confirm these findings and better define a possible role of UFT in maintenance therapy in some advanced non-metastatic HNSCC and NPC.