Evaluation of Nivolumab for Ototoxic Effects: An Animal Study in Rats

OBJECTIVES: The aim of this study was to assess whether nivolumab is ototoxic in rats and whether this ototoxicity is dose-dependent. MATERIALS and METHODS: Twelve rats were divided into two groups: Group 1 (control group, 6 rats, 12 ears) received intraperitoneal saline for 14 days. Group 2 (study...

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Published in:The Journal of the International Advanced Otology 2020, Vol.16 (2), p.218
Main Authors: Gulerl, Ismail, Kuzucu, Ihsan, Baklaci, Deniz, Kum, Rauf Oguzhan, Ucaryilmaz, Esra Ozhamam, Ozcan, Muge
Format: Report
Language:English
Subjects:
Chemotherapy
Comparative analysis
Nivolumab
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Summary:OBJECTIVES: The aim of this study was to assess whether nivolumab is ototoxic in rats and whether this ototoxicity is dose-dependent. MATERIALS and METHODS: Twelve rats were divided into two groups: Group 1 (control group, 6 rats, 12 ears) received intraperitoneal saline for 14 days. Group 2 (study group, 6 rats, 12 ears) and received two doses of 3 mg/kg intraperitoneal nivolumab within 14 days. Auditory brainstem responses (ABRs) were performed preoperatively and 4 and 8 weeks postoperatively. We compared between the groups, morphologic appearance of spiral ganglion cells and organ of Corti and density of spiral ganglion cells (measured with conventional light microscope connected to a personal computer). RESULTS: In our control group, both spiral ganglion and organ of corti had a normal morphological appearance. In our study group, spiral ganglion cells had a normal morphological appearance. However, some sections showed possibly mild degenerative changes in the organ of corti. Of 12 samples in the study group, four had a significant loss of density of spiral ganglion cells compared to the control group. The baseline ABR thresholds did not significantly differ between the groups (p=0.713). There was no statistically significant difference between the groups regarding ABR thresholds at week 4 (p=0.347). However, a statistically significant difference was observed in the ABR thresholds at week 8 (p=0.045). CONCLUSION: The results of our study showed that nivolumab treatment has ototoxic effects. Based on our results, we recommend monitoring the changes in the hearing ability of chemotherapy patients. KEYWORDS: Ototoxicity, nivolumab, immunotherapy, animal study
ISSN:1308-7649
DOI:10.5152/iao.2020.7123