Intratympanic N-acetylcysteine in the prevention of cisplatin-induced ototoxicity: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Objective: To evaluate the efficacy of the otoprotective transtympanic application of N-acetylcysteine in preventing chemotherapy-induced ototoxicity in patients subjected to platinum-based chemotherapy.

Data sources: PubMed, Scopus, Web of Science, Cochrane Central, and ClinicalTrials.gov were searched for the following concepts: (("Acetylcysteine" [Mesh]) AND ("Ototoxicity" [Mesh]) AND ("Cisplatin" [Objective: To evaluate the efficacy of otoprotective transtympanic application of N-acetylcysteine in the prevention of chemotherapy-induced ototoxicity in patients subjected to platinum-based chemotherapy. [Mesh]).

Study selection: Inclusion: randomized controlled trials, Exclusion: (1) case reports or case series; (2) thesis; (3) review articles; (4) conference abstracts; (5) animal studies; (6) non-english studies; (7) studies whose population was other than patients on platinum-based chemotherapy.

Data extraction: changes in hearing thresholds measured by pure tone tympanometry, covering high and low frequencies: 250, 500, 1000, 2000, 4000, and 8000 Hz. We used RevMan (Review Manager) version 5.3 to conduct the meta-analysis and GRADE to assess the quality of the evidence.

Data synthesis: The literature search yielded 277 unique articles. After reviewing six full-text articles, three RCTs provided data available for meta-analysis. A total of 88 cisplatin-based chemotherapy candidates were included for final analysis. Hearing thresholds showed a significant threshold difference between the ear treated with N-acetylcysteine and the control ear (ear not treated with N-acetylcysteine), especially at high frequencies as high as 8000 Hz (pooled effect size - 10.67, 95% CI [-12.33, -9.02], P < 0.00001). The data favored the Nac group in all frequencies as well, at 4000 Hz (pooled effect size - 2.13, 95% CI [-3.49, -0.77], P = 0.002), at 2000 Hz (pooled effect size - 1.38, 95% CI [-2.69, -0.06], P = 0.04), at 1000 Hz (pooled effect size - 1.58, 95% CI [-2.63, -0.53], P = 0.003), at 500 Hz (pooled effect size - 1.58, 95% CI [-2.62, -0.54], P = 0.003), and at the low frequency of 250 after solving the heterogeneity (pooled effect size - 0.96, 95% CI [-2.88, 0.95], P = 0.32).

Conclusions: Current data justifies the transtympanic administration of N-acetylcysteine for otoprotection in chemotherapy patients, minimizing the enduring consequences of cisplatin-induced ototoxicity and auditory impairment. Given the results' emphasis on the Sarafraz et al. (2018) study, more randomized controlled trials are necessary with an expanded sample size and standardization of N-acetylcysteine concentration, study population, and assessed outcomes.