Otoprotective measures for cisplatin-induced toxicity in chemoradiotherapy for head and neck cancer patients: a systematic review

Keywords

Cisplatin - Ototoxicity - Chemoradiotherapy - head and neck neoplasms

This systematic review was conducted to identify otoprotective measures and treatments for ototoxicity induced by high-dose Cisplatin-based concurrent chemoradiotherapy (CRT) administered as adjuvant, or definitive, therapy in head and neck cancer (HNC) patients. The review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed Central, Medline, and SciELO databases were used as sources in March 2024. The inclusion criteria were prospective or retrospective cohort studies, case-control studies, and phase II or III trials published in English, with full-text availability, which analyzed ototoxicity following otoprotective measures or treatments in high-dose Cisplatin-based CRT (100 mg/m² intravenous every 21 days) for HNC patients. Article selection was performed independently by three analysts, covering database searches, duplicate removal, and relevant article selection. Out of 216 initially identified articles, 11 were assessed in the final analysis: four involving low-dose Cisplatin-based CRT (three at 40 mg/m² IV weekly and one at 20 mg/m² IV weekly), three utilizing high-dose intra-arterial Cisplatin-based CRT and Sodium Thiosulfate, one study with intratympanic Sodium Thiosulfate administered before high-dose Cisplatin-based CRT, one involving Nedaplatin-based CRT, one with intratympanic Dexamethasone prior to weekly Cisplatin-based CRT, and one with Acetylcysteine administered before high-dose Cisplatin-based CRT. Most intervention did not show a statistically significant reduction in ototoxicity compared to high-dose Cisplatin-based CRT alone. Statistically significant reductions in ototoxicity were observed in only one out of the three studies using high-dose intra-arterial Cisplatin-based CRT with Sodium Thiosulfate, the study with Nedaplatin-based CRT, and the study with intratympanic Dexamethasone prior to weekly Cisplatin-based CRT. The only strategy demonstrating lower ototoxicity rates and comparable survival outcomes to high-dose Cisplatin-based CRT was low-dose Cisplatin-based CRT. Our systematic review identified a limited number of studies on otoprotective measures for high-dose Cisplatin-based CRT, with most studies showing negative results, small patient populations, and low-quality standards. The only measure showing a trend toward reducing ototoxicity while maintaining similar survival data to the high-dose Cisplatin-based CRT was the use of low-dose Cisplatin-based CRT.

Corresponding author: Katia Regina Marchetti (e-mail: [e-mail]).

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
06 May 2025