Assessment and Management of Platinum-Related Ototoxicity in Children Treated for Cancer

Abstract

Platinum compounds are a group of chemotherapeutic agents included in many pediatric and adult oncologic treatment protocols. The main platinum compounds are cisplatin, carboplatin, and oxaliplatin. Their use in clinical practice has greatly improved long-term survival of pediatric patients, but they also cause some toxic effects: ototoxicity, myelosuppression, nephrotoxicity, and neurotoxicity. Hearing damage is one of the main toxic effects of platinum compounds, and it derives from the degeneration of hair cells of the ear, which, not having self-renewal capacity, cannot reconstitute themselves. Hearing loss from platinum exposure is typically bilateral, sensorineural, and permanent, and it is caused by the same mechanisms with which platinum acts on neoplastic cells. According to available data from the literature, the optimal timing for the audiological test during and after treatment with platinum compounds is not well defined. Moreover, no substances capable of preventing the onset of hearing loss have been identified.

Keywords: cancer; chemotherapy; children; ototoxicity; platinum compound.

Figure 1

In (A) a schematic representation of a transverse section of the basal part of a mammalian cochlea. Organ of Corti cellular organization: one inner hair cell (IHC) and three outer hair cells (OHCs) are represented on either side of the tunnel of Corti. The tectorial membrane, floating in endolymph, caps the tallest stereocilia of the hair cells. The IHC is surrounded by supporting cells, whereas OHCs are anchored to the Deiters’ cells, their lateral membrane in direct contact with a fluid called endolymph, which fills the tunnel of Corti. The lateral wall is constituted by the stria vascularis and spiral ligament. In (B), representative images are shown of surface preparations of the organ of Corti stained for F actin, used to visualize the stereociliary arrays and cuticular plates of hair cells. The dark spots indicated by asterisks in (C) show OHC loss after a single dose of cisplatin in the rat model.