N-acetylcysteine for the Prevention of Cisplatin-Induced Hearing Loss: A Systematic Review and Meta-analysis.

Objective: Cisplatin is an effective antineoplastic drug used worldwide in the treatment of various malignancies. However, it is associated with side effects, including cisplatin-induced hearing loss (CIHL). N-acetylcysteine (NAC) has been suggested as a promising drug to prevent or reduce cisplatin-derived ototoxicity. To evaluate the evidence supporting the efficacy of NAC in preventing CIHL, we conducted a systematic review and meta-analysis of the literature.

Data sources: A systematic search was conducted on PubMed, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library.

Review methods: Articles reporting the administration of systemic or transtympanic injection of NAC for CIHL prevention were considered. The outcomes of interest included the presence of hearing loss events and changes in hearing thresholds at 0.5 through 12 kHz following cisplatin treatment.

Results: A total of 7 studies involving 217 patients met inclusion criteria. Of these patients, 175 received systemic administration of NAC, and the remaining received transtympanic injection of NAC. No significant differences were found in CIHL prevention between the use of either systemic or transtympanic NAC administration compared to placebo (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.54-1.19; P = .28, and RR 0.89; 95% CI 0.51-1.54; P = .67, respectively). No significant differences were found at 0.5 to 8 kHz between groups. Qualitative analyses suggested a tendency to otoprotection in ultra-high frequencies (10 and 12 kHz).

Conclusion: Our findings suggest that, regardless of administration route, current published evidence does not show that NAC is effective in preventing CIHL in the standard clinical audiogram range. Further studies with larger samples are needed to confirm our findings.

Level of evidence: I.