Cisplatin-induced ototoxicity: audiometric findings and experimental cochlear pathology

Twenty-four (48%) out of a group of 50 patients treated with one to three single doses of cisplatin compound (cis-DDP), at a dosage of 60 mg/m2 body surface, were found to have deterioration of post-treatment pure tone audiometric threshold levels. Statistical analysis of pre- and post-treatment hearing losses by means of the paired t-test, however, did not show any significant hearing loss associated with cis-DDP-toxicity, nor could hearing loss following treatment be correlated to ages of the patients, pre-treatment hearing impairments, specific frequencies, or the number of treatment courses given. In contrast, cochlear damage was studied in the guinea pig model by daily administration of high cumulative doses of cis-DDP, and was found to be dose-dependent and selectively restricted to the outer hair cells of the inner ear and corresponding nerve fibers. Hair cell degeneration was most severe in the basal turn of the cochlea, and progressed in an apical direction so that the cells in the first row were the most affected.