Future opportunities in preventing cisplatin induced ototoxicity

Area of Science:

• Ototoxicity research
• Cancer therapy side effects
• Reactive oxygen species (ROS) in inner ear damage

Background:

• Cisplatin is a widely used chemotherapy drug.
• Otototoxicity (hearing damage) is a significant dose-limiting side effect of cisplatin.
• Cisplatin is thought to induce ototoxicity by suppressing endogenous antioxidants, leading to reactive oxygen species (ROS) damage in the inner ear's outer hair cells (OHCs).

Purpose of the Study:

• To review strategies for preventing cisplatin-induced ototoxicity.
• To discuss the translation of promising chemoprotective agents from animal models to clinical practice.
• To explore systemic and transtympanic administration routes for otoprotective agents.

Main Methods:

• Review of existing literature on cisplatin ototoxicity and otoprotective agents.
• Analysis of challenges in clinical translation, including systemic administration effects on anti-tumor activity and transtympanic diffusion across the round window membrane (RWM).
• Evaluation of animal model successes and their potential clinical applicability.

Main Results:

• Amifostine, an antioxidant tested for otoprotection, yielded disappointing clinical trial results.
• Numerous agents have shown chemoprotective effects against cisplatin-induced ototoxicity in animal models.
• Successful clinical application requires agents that do not compromise cisplatin's anti-tumor efficacy and efficient delivery methods (systemic or transtympanic).

Conclusions:

• Translating effective otoprotective strategies from animal studies to human clinical practice is essential.
• Optimizing administration routes, considering drug diffusion across the RWM for transtympanic delivery, is critical.
• Successful otoprotectors could enhance cisplatin therapy effectiveness and improve patient quality of life.