Background/Aim: This study evaluated the utility of the histamine H2-receptor antagonist lafutidine in patients taking oral fluorouracil (S-1) for head and neck squamous cell carcinoma (HNSCC), by comparing patients with and without concomitant lafutidine. Patients and Methods: Study subjects comprised 63 patients who received adjuvant S-1 following curative resection of HNSCC at our institutions between August 1, 2013 and December 31, 2019. The primary endpoint was the completion rate of S-1 therapy. Results: For the lafutidine-treated group, the median completion rate was significantly greater (94.4% vs. 24.6%, p=0.01), and progression-free and overall survival were both significantly prolonged compared to the non-lafutidine group. In terms of adverse events, the incidence of diarrhoea was significantly reduced (p<0.00189) in the lafutidinetreated group. Conclusion: Taking lafutidine during S-1 treatment appeared to reduce gastrointestinal disturbance and increased the S-1 completion rate, improving both progression-free and overall survival as a result.Curative treatment for locally advanced head and neck cancer has conventionally involved a combination of surgery and radiotherapy (1). Because the head and neck region not only carries out functions that play crucial roles in daily life, but is also an important site cosmetically, recent years have seen attempts to use concurrent chemoradiotherapy as curative treatment, with the goal of sparing organs and their functions.In cases of advanced cancer, however, the prognosis cannot be considered satisfactory, even for patients who have undergone curative therapy, and adjuvant chemotherapy following curative treatment is reportedly useful (1, 2).Two large-scale Japanese studies of adjuvant chemotherapy for advanced head and neck cancer have been reported. The first, a comparative trial conducted by Tsukada et al., administered tegafur and uracil (UFT) to patients for 1 year following curative therapy for head and neck cancer (3). The study incIuded patients with I-IV primary squamous cell carcinoma of the head and neck with no distant metastasis. Although both the 3-year overall survival (OS) rate (UFT group, 77.9%; untreated group, 72.9%) and 3-year relapse-free survival rate (UFT group, 73.4%; untreated group, 66.2%) tended to be better in the UFT-treated group, the difference was not significant. The distant recurrence rate, however, was significantly lower in the UFT group (7.9% vs. 14.6%, respectively; p=0.034), suggesting that UFT is useful as adjuvant chemotherapy.The second large-scale study was the ACTS-HNC study by Tsukahara et al., as a comparative trial of S-1 and UFT (4). Both 3-year disease-free survival and 3-year relapse-free survival tended to be better in the S-1-treated group, and OS was significantly better (p=0.022). However, the incidence of mucositis/stomatitis as an adverse event was significantly higher in the S-1 group than in the UFT group. The 1-year completion rate for S-1 was low, at 43%, and control of adverse events was conjectured ...