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.