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Introduction: In the absence of a published head-to-head trial between concomitant cisplatin-radiotherapy vs cetuximab-radiotherapy, we compared results of cetuximab vs cisplatin in unresectable HNSCC in our daily clinical practice. Materials and methods: We retrospectively analyzed all consecutive patients with unresectable HNSCC treated at Clinical Oncology Unit of the University Hospital of Ferrara (Italy) from October 2008 to February 2010. Results: We evaluated 21 patients: at last follow-up, 6 patients (28.6%) were deceased, 15 patients (71.4%) were alive and, among these, 13 (61.9%) were alive without evidence of disease (NED). Median follow-up time was 9.74 months. Median OS was 10.95 months. General characteristics were similar in the two subgroups, except for median age (low in cisplatin-subgroup: 55 vs 72) and the type of response (with a high numbers of complete response in cisplatin-subgroup). By the univariate analysis there was no statistical significance difference in OS (p= 0.898) between the two subgroups. Conclusions: Based on state-of-the-art, it was not possible to identify either treatment regimen is as superior in prolonging either locoregional control or OS: our results seem to indicate that the two treatments may be equally efficacious and deferring the choice of treatment on the toxicity profile. Head-to-head trials are needed. [ABSTRACT FROM AUTHOR]