Cisplatin: evaluation of its ototoxic potential.

The ototoxic potential of cisplatin was analyzed in an organ culture model exposing the hair cells and other inner ear structures to cisplatin doses from 0.1 to 10 micrograms/ml. Selective hair cell degeneration was obvious at concentrations of 0.1 microgram/ml. Incubation with 1 microgram/ml caused morphologic damage in the supporting cells in both the cochlear and vestibular parts of the labyrinth. Exposure to 10 micrograms/ml during five days caused a total collapse of the membranous labyrinth. The morphologic degeneration pattern at the ultrastructural level is nonspecific, except that nuclear chromatin was either swollen and disintegrated or considerably condensed. Based on inner ear concentrations equivalent to aminoglycoside antibiotics in the range of 0.1 to 10 micrograms/ml, cisplatin is, in the in vitro model used in this study, the most ototoxic drug known. However, because of its single dose administration and long intervals between administration, clinical ototoxicity is less pronounced than that from aminoglycoside antibiotics.