Objectives: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL). DESIGN Randomized... Show moreObjectives: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL). DESIGN Randomized controlled trial. SETTING Tertiary cancer hospital. PATIENTS Adults to be treated with high-dose cisplatin (>= 75 mg/m(2)). INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration. After amendment, the placebo ear was left untreated. Main Outcome Measure: Primary outcome was safety and feasibility. Secondary outcomes included pharmacokinetic analysis of systemic cisplatin and preliminary activity of STS. Clinically relevant CIHL was defined as a >= 10 dB threshold shift at pure-tone average 8-10-12.5 kHz (PTA(8-12.5)). Response to STS was defined as a threshold shift at PTA(8-12.5) in the STS-treated ear of >= 10 dB smaller than the untreated ear. Results: Twelve patients were treated. Average CIHL at PTA(8-12.5) was 12.7 dB in untreated ears and 8.8 dB SPL in STS-treated ears (p = 0.403). Four patients did not develop CIHL. Four out of eight patients with CIHL responded to STS: CIHL at PTA(8-12.5) in STS-treated ears was 18.4 dB less compared to untreated ears (p = 0.068). Grade 1 adverse events were reported. Pharmacokinetic results were available for 11 patients. Conclusion: Transtympanic application of STS was safe and feasible. Based on our pharmacokinetic analysis, we postulate that transtympanic STS does not interfere with the systemically available cisplatin. Our results provide a preliminary proof of concept for transtympanic application of STS in preventing CIHL and warrants further evaluation on a larger scale. Show less