Effect of sodium thiosulfate anhydrous on cisplatin-induced ototoxicity in pediatric cancers: Turkish compassionate use treatment protocol—Updated results.

Abstract

e15075 Background: Cisplatin induced ototoxicity (CIO), with permanent hearing loss is observed in >60% pediatric patients in Turkey. PEDMARK (Sodium Thiosulfate anhydrous) reduced the risk of CIO cases with non-metastatic solid tumors observed in Phase 3 studies (SIOPEL 6 & COG ACCL0431). We aimed to evaluate the investigational product PEDMARK provided for pediatric cases via a National Compassionate Use Treatment Protocol (CUP) in Turkey. Methods: Patients (1 month to <18 years) with a localized, nonmetastatic solid tumor, standard-risk hepatoblastoma (HBB), nasopharyngeal carcinoma (NPC) and medulloblastoma MB whose treatment plans were including cisplatin were eligible. PEDMARK was administered intravenously 6 hours after each cisplatin dose infusion. Adverse events, demography, pre and post- hearing were recorded from 21OCT2019-21SEPT2022. Results: The CUP enrolled 12 patients, 8 HBB, 3 NPC and 1 MB in 3 years, from 6 academic institutions. HBB patients' median age was 1year (3mos-3 yrs). All pts had newly diagnosed HBB PRETEXT 3 (n = 5) with a median baseline AFP OF 54.000. 3 NPC age 13-17 yrs, MB 6yrs of age. All patients had Brock Grade 0 on hearing tests prior to treatment Patients received a median 0f 6 cycles (range 4-6) of cisplatin and PEDMARK. Patients with hearing tests available post-treatment (n=11), all maintained Brock Grade 0. At a median of 0.8mos post-treatment, CR were observed in all patients except one HBB with progressive disease. All CRs wer sustained 18.8 mos. AEs in 2 patients were Grade 1-2 nausea/vomiting, no Grade >3 AEs were reported. Conclusions: PEDMARK was well tolerated, provided via a Turkish CUP to reduce the CIO in pediatric patients with nonmetastatic solid tumors. No hearing loss was observed/ detected post-treatment and the tumor outcomes were consistent with the Phase 3 studies. This is very encouraging.