Prevention and treatment of cisplatin‐induced ototoxicity in adults: A systematic review

Abstract

ObjectivesOtotoxicity is a common disabling side effect of platinum‐based chemotherapy. This study aimed to assess the evidence on the management of platinum‐induced ototoxicity in adult cancer patients.MethodsFour databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non‐pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.ResultsNineteen randomised controlled trials and five quasi‐experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non‐pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D‐methionine) showed mild benefits in preventing cisplatin‐induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention‐related adverse effects, thereby limiting safety conclusions.ConclusionsCurrent interventions have mild benefits in preventing cisplatin‐induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high‐quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.

The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds

“…To overcome the two main problems associated with cisplatin treatment, namely severe side effects and resistance, a number of approaches for the design and implementation of platinum-based drugs capable of being activated on-site in the tumor tissue have been developed. For example, classes of kinetically inert platinum-based anticancer prodrugs, suitable for on-site transformation to more reactive platinum(II) species, either leveraging the reducing environment in solid tumors, or activated on site through phototherapy, have been developed [249,250].…”

“…Furthermore, trans-configured oxime-liganded platinum complexes, which displayed many attributes different from those of established anticancer agents, including a distinct DNA binding behavior, increased cellular accumulation, and an unusual pattern of protein interaction, have gained traction as a new class of anticancer therapies [248,249,251]. As a result, a number of platinum(II) oxime complexes, inert at physiological pH, but capable of being activated into their cytotoxic platinum forms under a slightly acidic pH environment, have been developed [252][253][254][255][256], and some illustrative examples are provides in Figure 18.…”