Optimizing Outcomes in Elderly HNSCC : Efficacy of UFT Metronomic Therapy

Introduction Head and neck squamous cell carcinoma (HNSCC) remains a significant clinical challenge, especially in elderly patients with advanced‐stage disease and multiple comorbidities. Metronomic chemotherapy with oral tegafur‐uracil (UFT) offers a low‐toxicity maintenance option that may improve outcomes. This study aimed to evaluate the efficacy and tolerability of UFT as metronomic therapy in elderly patients with nondistant metastatic stage III/IV HNSCC. Materials and Methods This retrospective study included patients aged ≥ 70 years diagnosed with non‐distant metastatic stage III/IV HNSCC between January 1, 2008 and December 31, 2023 at a single center. Patients were divided into two groups: those receiving metronomic UFT following initial treatment (UFT group) and those without UFT (non‐UFT group). The primary outcomes were progression‐free survival (PFS) and overall survival (OS). Multivariate Cox regression analysis was used to assess the impact of UFT on survival outcomes. Results A total of 103 patients were included, with 40 in the UFT group and 63 in the non‐UFT group. The UFT group showed significantly longer PFS (median: 24.6 vs. 7.2 months, p = 0.0011) and OS (median: 26.0 vs. 9.6 months, p = 0.012). Multivariate analysis confirmed the independent association of UFT with improved PFS and OS. Conclusions Metronomic UFT was associated with improved PFS and OS in elderly patients with advanced HNSCC and was well tolerated, with all adverse events limited to grade 1–2. Landmark analysis confirmed that the observed benefit was not attributable to immortal time bias. These exploratory findings warrant validation in prospective studies.