Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model

Objective Programmed cell death protein-1 (PD-1) inhibitors that have been recently introduced for the systemic treatment of head and neck cancers offer the advantage of fewer side effects and more effective treatment than chemotherapy drugs. A review of the literature shows that the ototoxic side effects of the PD-1 inhibitor have not yet been fully elucidated. In this study, we aimed to investigate whether the PD-1 inhibitor has ototoxic activity using both electrophysiological and histopathological methods. Methods A total of 24 rats, 12 for the study group, and 12 for the control group were included in the study. The study group was administered the PD-1 inhibitor. The auditory brainstem responses (ABR) of the study and control groups were evaluated. At the end of the study, all animals were sacrificed, and their cochleae were examined by immunohistochemical staining. Results In the study group, the ABR values ​​were 13.95 ± 2.70 before treatment, 15.83 ± 1.94 at week 4 of treatment (p=0.024), and 15.00 ± 1.06 at week 7 (p=0.157). Furthermore, according to immunohistochemical staining, the cochlear hair cells were reduced in the study group compared to the control group. Conclusion It was determined that the PD-1 inhibitor showed ototoxic activity during the course of treatment, but this was spontaneously resolved during follow-up. The clinical significance of these findings should be supported by human studies.