Abstract
ObjectiveProgrammed 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.MethodsA 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.ResultsIn 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.ConclusionIt 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.
Highlights
Squamous cell carcinoma of the head and neck (SCCHN) is a malignancy that causes more than 300,000 deaths worldwide every year
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
Categories: Otolaryngology Keywords: programmed cell death protein-1, pembrolizumab, ototoxicity, rat Squamous cell carcinoma of the head and neck (SCCHN) is a malignancy that causes more than 300,000 deaths worldwide every year
Summary
Squamous cell carcinoma of the head and neck (SCCHN) is a malignancy that causes more than 300,000 deaths worldwide every year. SCCHN treatment usually requires a multidisciplinary approach involving surgery, radiotherapy, and systemic medical therapy [1]. Advancements in systemic treatment modalities have led to the development of programmed cell death protein-1 (PD-1) inhibitors that have the advantages of being more effective in appropriate indications and offering a more comfortable treatment with fewer side effects compared to chemotherapy drugs [1,2,3]. Antibodies that block PD-1 ligation, such as pembrolizumab, have recently been introduced in the treatment of SCCHN, non-small cell lung cancer, kidney cell cancer, and melanoma [4]. In patients with SCCHN, the side effects of pembrolizumab therapy have been reported as fatigue, pruritus, rash, diarrhea, elevated liver function, hyponatremia, heart failure, hypothyroidism, adrenal insufficiency, and myositis [5]
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