COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss

Abstract

BackgroundCisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy.MethodsA total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears.ResultsAlthough aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL.ConclusionsAspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here.

Protection for medication-induced hearing loss: the state of the science

“…These studies did show significant reduction in hearing loss in the treatment groups, no negative impacts to gentamicin therapy, but notable gastric side effects (gastric bleeding), which is a known risk factor for aspirin treatment paradigms (Sha, Qiu, and Schacht 2006). Additionally, a phase II study of the efficacy of salicylate in reduction of cisplatin-induced ototoxicity did not yield oto-protective results, although it was well tolerated (Crabb et al 2017). As such, use of salicylate requires more research to determine the safety profile and optimised dosing for each ototoxic insult.…”

Antioxidant Therapy against Oxidative Damage of the Inner Ear: Protection and Preconditioning

“…A meta-analysis also showed the potential of aspirin administration for the prevention of ototoxicity based on the paradoxical effect of aspirin [107]. In contrast, aspirin failed to show a significant protective effect against ototoxicity in a multi-center randomized trial [108]. Therefore, further research is required to verify the effects of aspirin on ototoxicity.…”

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

“…Clinical trials in humans have compared other ototoxic drugs such as aminoglycosides that also have an important association with ROS production. As the case of aspirin, which had a protective effect against gentamicin, but when its clinical benefits were tested in 94 patients undergoing cisplatin the cumulative dose of 200mg / m2 no significant effect was reported [44] (Table 1).…”