Efficacy and Safety of Cisplatin Versus Carboplatin for Patients With Squamous Cell Carcinoma of Head and Neck: A Systematic Review and Meta‐Analysis

ABSTRACT Background Cisplatin‐ and carboplatin‐based regimens are widely used in the treatment of head and neck squamous cell carcinoma (HNSCC), yet comparative evidence on survival and toxicity outcomes remains limited. While cisplatin is standard in many settings, carboplatin is often preferred in patients with comorbidities or impaired renal function. This systematic review and meta‐analysis aimed to synthesize available evidence comparing cisplatin versus carboplatin in HNSCC. Methods A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library from inception to February 2026. Randomized and observational studies comparing cisplatin‐ and carboplatin‐based regimens in HNSCC were included. Primary outcomes were overall survival (OS), progression‐free survival (PFS), locoregional recurrence‐free survival at 1, 3, and 5 years and distant metastasis‐free survival (DMFS) at 1 and 3 years. Secondary outcomes include grade ≥ 3 toxicities. Data were pooled using random‐effects meta‐analysis. Results Eight studies comprising 1044 patients were included, including four recently published studies not previously pooled in head‐to‐head analyses. Pooled analyses showed no statistically significant differences between cisplatin and carboplatin in OS, PFS, LRRFS, or DMFS overall. Subgroup analyses across 1, 3, and 5‐year follow‐up intervals likewise demonstrated no significant differences for most outcomes. The only significant finding was a modest difference in 5‐year LRRFS favoring cisplatin, based on only two studies. No statistically significant differences were observed in grade ≥ 3 anemia, leukopenia, thrombocytopenia, or nausea/vomiting. Conclusions Cisplatin and carboplatin‐based regimens yield largely comparable survival and toxicity outcomes in HNSCC. Treatment selection should be guided by patient comorbidities and tolerability.