Effects of delayed sodium thiosulfate on cisplatin-induced ototoxicity in pediatric and adolescent patients with cancer: Results from the Japanese Children’s Cancer Group STS-J01 study.

10052 Background: Cisplatin is a cornerstone of therapy for pediatric, adolescent, and adult solid tumors but frequently causes irreversible, dose-dependent ototoxicity. Delayed administration of sodium thiosulfate (PEDMARK) has demonstrated otoprotection in Western trials. STS-J01 evaluated the efficacy, safety, and pharmacokinetics of delayed sodium thiosulfate anhydrous in Japanese pediatric and adolescent patients. Methods: STS-J01 was an open-label, single-arm phase II study enrolling patients aged 0–18 years with localized solid tumors receiving cisplatin-based chemotherapy. Sodium thiosulfate (12.8 g/m²) was administered intravenously 6 hours after completion of each cisplatin dose. The primary endpoint was incidence of hearing loss by American Speech-Language-Hearing Association (ASHA) criteria in patients aged ≥3 years, compared with the observational cohort of ACCL0431. Secondary endpoints included hearing loss by Brock classification, tumor response, safety, and pharmacokinetics. Results: Thirty-one patients were enrolled, including 25 evaluable patients in the primary cohort (Table). Hearing was preserved in the majority of patients, with 76% free of ototoxicity by ASHA criteria and 84% with no hearing loss by Brock classification, representing a significant reduction versus historical controls (relative risk 0.42; 95% CI 0.20–0.82; P=0.007). Antitumor efficacy was preserved, with an objective response rate of 95.8% and there was no evidence of treatment interference from sodium thiosulfate. Pharmacokinetic analyses demonstrated no clinically meaningful impact of sodium thiosulfate on cisplatin exposure. No serious adverse events were attributed to sodium thiosulfate transient electrolyte abnormalities were manageable and reversible. Conclusions: Delayed administration of sodium thiosulfate significantly reduced cisplatin-induced ototoxicity without compromising antitumor efficacy in Japanese pediatric and adolescent patients, confirming reproducibility of sodium thiosulfate otoprotection across populations. Clinical trial information: jRCT2061220018. Summary of STS-J01 trial. Age at diagnosis (years) 3–6 (N=4) 7–14 (N=17) 15-18 (N=4) Total (N=25) No Hearing Loss by ASHA 2/4(50%) 13/17 (76.4%) 4/4 (100%) 19/25 (76.0%) Disease Hepatoblastoma 1/2 (50%) - - 1/2 (50.0%) Germ Cell Tumors 1/1 (100%) 6/6 (100%) 1/1(100%) 8/8 (100%) Bone and Soft Tissue Tumors - 6/8 (75.0%) 3/3 (100%) 9/11 (81.8%) Medulloblastoma 0/1 (0%) 0/1 (0%) - 0/2 (0%) Others - 1/2 (50.0%) - 1/2 (50.0%) Chemotherapy Responder* 4/4 (100%) 16/16 (100%) 3/4 (75.0%) 23/24 (95.9%) *One case was unevaluated for treatment response.