Clinical trials evaluating transtympanic otoprotectants for cisplatin-induced ototoxicity: what do we know so far?

Association of Sodium Thiosulfate With Risk of Ototoxic Effects From Platinum-Based Chemotherapy

“…To avoid the potential influence on the antitumor function of platinum, the transtympanic approach of STS has been investigated and has shown some efficacy in studies, mainly by the ability to form inactive complexes and prevent the release of cytochrome C in the inner ear. 26 , 45 , 46 However, in the subgroup analysis of our study, we found that intravenous administration of STS was associated with an otoprotective outcome, while there was a decrease in ototoxic effects with administration via transtympanic injection, although this difference was not statistically significant. Various factors may attenuate the association of STS with otoprotective outcomes by transtympanic delivery.…”

“…First, the permeability of the drug solution could be easily cofounded by other factors, including viscosity, environmental pH, or even the use of a facilitating agent. 46 , 47 Second, because the administration would inevitably pass through the middle ear, lesions in the middle ear, such as effusions, would certainly influence the efficacy of STS. In the included study 25 that enrolled patients undergoing the transtympanic approach of STS delivery, all patients had head and neck cancer and received concurrent chemoradiation therapy over the head and neck area.…”

Oxidative Stress and Inflammation Caused by Cisplatin Ototoxicity

“…For adults receiving cisplatin, the transtympanic approach appears to be attractive. However optimal dose, number of injections and clarifying what protectant is the safest and most effective would be important factors for consideration [ 105 ]. A novel formulation of sodium thiosulfate appears to be well tolerated and safe.…”

The Effect of Otoprotective Substances Against Cisplatin Exposure: A Literature Review

“…Excessive ROS can induce apoptosis through extrinsic and intrinsic pathways. Cellular stress, such DNA damage, results in the release of cytochrome-c from the mitochondria causing activation of procaspase-9 through the interaction with apoptosis promoting activation of factor-1 and formation of an active apoptosome complex [9].…”

“…However, the risk of ototoxic and nephrotoxic side effects commonly hinders the use of higher doses that could otherwise maximize its antineoplastic effects [8]. Clinically, cisplatin induced ototoxicity appears generally as a progressive, bilateral and irreversible sensorineural hearing loss at high frequencies and progresses towards the lower frequencies [9].…”