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Background Triweekly high‐dose cisplatin (100 mg/m2) with concurrent radiation therapy is the current standard of care in the definitive or appropriate postoperative setting in head and neck squamous cell carcinoma (HNSCC). We compared triweekly 100 mg/m2 with alternative weekly 40 mg/m2 and weekly <40 mg/m2 cisplatin regimens. Methods From 2011 to 2016, 163 patients received concurrent cisplatin and intensity‐modulated radiotherapy for locally advanced HNSCC. Primary endpoints were overall survival (OS) and progression‐free survival. Results Cisplatin weekly <40 mg/m2 showed inferior OS outcomes when compared to weekly 40 mg/m2 (P = 0.084) and triweekly 100 mg/m2 (P = 0.04) regimens. Conclusion Our study displayed inferior outcomes with weekly cisplatin doses under 40 mg/m2, suggesting the inferiority of low‐dose weekly chemotherapy and the need for ongoing randomized trials to further explore 40 vs 100 mg/m2 chemotherapy regimens.

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