Adverse event profiles and management of cisplatin-based chemoradiotherapy in locally advanced head and neck squamous cell carcinoma: a systematic review

Background: Patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) are treated with curative intent. Treatment guidelines recommend tumor resection, followed by adjuvant radiotherapy or chemoradiotherapy in patients with high risk of disease recurrence, or definitive chemoradiotherapy in patients who do not undergo surgery. When indicated, concurrent cisplatin provides benefit over radiotherapy alone but is highly toxic. In this systematic literature review, we review adverse event (AE) profiles of cisplatin based chemoradiotherapy in patients with LA SCCHN and synthesize AE management strategies based on expert clinical opinion. Methods: PubMed and Google Scholar were searched for relevant articles published between January 1, 2000, and January 9, 2024. Eligible articles characterized AE profiles associated with cisplatin-based chemoradiotherapy. Data on the percentage of patients with AEs were compared across cisplatin regimens. Results: We reviewed 53 articles reporting on 51 studies. Cisplatin 40 mg/m2 weekly (QW) was more tolerable than cisplatin 100 mg/m2 every 3 weeks (Q3W), incurring less acute grade 3-5 neutropenia, hepatotoxicity, nephrotoxicity and related electrolyte imbalances, and tinnitus in the postoperative setting, but cisplatin QW led to more frequent thrombocytopenia and pain. Conclusion: The relative efficacy of cisplatin Q3W versus QW remains under investigation. Cisplatin QW inherently increases the cumulative cisplatin dose more gradually, which may help in managing certain AEs. Treatment guidelines should be updated on the management of challenging AEs, including more detailed criteria on topics such as management of kidney failure including dialysis and timing of feeding tube placement.