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Background/Aims We investigated the efficacy and toxicity of a weekly schedule of docetaxel and cisplatin as a first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Methods In this study, 18 patients with previously diagnosed R/M HNSCC were treated with combination chemotherapy of weekly docetaxel 35 mg/m2 (day 1 and 8) and cisplatin 70 mg/m2 (day 1) as first-line chemotherapy, repeated every 3 weeks. Results Partial response and stable disease were observed in six patients (33.3%; 95% confidence interval [CI], 11.1% to 55.6%) and six patients (33.3%; 95% CI, 11.1% to 55.6%), respectively. The median overall survival and progression-free survival were 11.26 months (95% CI, 8.87 to 15.83) and 5.68 months (95% CI, 4.80 to 6.51), respectively. The major toxicity was grade 1/2 anemia (50%). Grade 3/4 neutropenia was observed in one patient (5.6%). Among the non-hematologic toxicities, grade 1/2 hepatotoxicity was most common (22.2%), and grade 3/4 infection was observed in one patient (5.6%). There was no treatment-related mortality. Conclusions For patients with R/M HNSCC, a cisplatin and weekly docetaxel regimen showed high efficacy with tolerable toxicity as a first-line treatment.