Simple SummaryMany head-and-neck cancer patients assigned to chemoradiation cannot receive concurrent cisplatin due to impaired renal function. Carboplatin may be an alternative option. We compared the chemoradiation outcomes of 131 patients who received cisplatin vs. 45 patients who were unfit for cisplatin and received carboplatin. Both groups were compared for loco-regional control, metastases-free survival, overall survival, toxicities, and the completion of chemotherapy. Patients receiving carboplatin were significantly older and had more G3 tumors; the other characteristics were balanced. No significant differences were found regarding loco-regional control, metastases-free survival, overall survival, and toxicities. Non-significantly more patients assigned to carboplatin completed their chemotherapy as planned. Given the limitations of this study, carboplatin appears a reasonable option for patients who require chemoradiation but cannot receive cisplatin.AbstractCisplatin is the standard for the chemoradiation of squamous cell carcinoma of the head and neck (HNSCC). Many patients cannot receive cisplatin due to impaired renal function. This study investigated carboplatin as an alternative option. In total, 131 patients assigned to two courses of cisplatin (20 mg/m2/d1-–5 or 25 mg/m2/d1–4) were matched to 45 patients not suitable for cisplatin and receiving carboplatin (AUC 1.0/d1–5 or AUC 1.5/d1–4). The endpoints included loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS), toxicities, and the completion of chemotherapy. The patients in the carboplatin group were significantly older and had more G3 tumors. Otherwise, the baseline characteristics were balanced. The LRC rates at 2 and 3 years were 77% and 76% in the cisplatin group vs. 69% and 65% in the carboplatin group (p= 0.21). The MFS rates were 83% and 78% vs. 78% and 74% (p= 0.34) and the OS rates 83% and 79% vs. 83% and 75% (p= 0.64), respectively. The outcomes were not significantly different in the subgroups receiving definitive or adjuvant chemoradiation. No significant differences were found regarding toxicities. Non-significantly more patients in the carboplatin group completed their chemotherapy (78% vs. 66%,p= 0.15). Carboplatin was associated with similar outcomes and toxicities as cisplatin, although these patients had worse renal function, more aggressive tumors, and were older. Given the limitations of this study, carboplatin appears an option for patients not suitable for cisplatin.