{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:00:51Z","timestamp":1784714451182,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015525","name":"Otonomy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015525","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cisplatin\u2010induced hearing loss (CIHL) remains a significant complication of pediatric cancer treatment. We evaluated the feasibility, safety, and trends of the efficacy of intratympanic injections of sustained\u2010exposure dexamethasone thermosensitive gel (OTO\u2010104) for otoprotection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>In this multisite randomized phase 2 trial (NCT02997189), patients aged 0.5\u201321 years with newly diagnosed cancer treated with cisplatin were eligible. Participants\u2019 ears were randomized to receive up to three intratympanic injections of 0.2\u00a0mL OTO\u2010104 in one ear and no treatment contralaterally. OTO\u2010104 was administered by an otolaryngologist within 72 hours preceding each cisplatin cycle. Feasibility was determined by the successful administration of intended doses. Treatment\u2010emergent adverse events (TEAEs) and outcomes were monitored by physical examination, concurrent medications, otoscopy, tympanometry, and audiometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From January 6 to September 26, 2017, 18 doses of OTO\u2010104 were administered to 11 evaluable participants across 5 centers (range, 1\u201314 years; 9 neuroblastoma and 2 osteosarcoma) via intratympanic injection (9) or tympanostomy tube (2). Sixteen injections were paired with other procedural sedations and two were performed awake; all injections were successfully delivered. The median interval between OTO\u2010104 and cisplatin was 14 hours (range, 7\u201364). Clinically insignificant tympanic scabs were noted in five participants; no middle ear changes were observed. There were three otologic TEAEs (two transient mild\u2010moderate otalgia [related] and one hypoacusis [unrelated]) and no related non\u2010otologic TEAEs. CIHL developed similarly in treated versus untreated ears; the trial was terminated early.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although dexamethasone at this dose was not otoprotective, these results suggest that intratympanic injection may be safe, feasible, and a viable delivery platform for testing other otoprotectants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31680","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T08:45:44Z","timestamp":1742978744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Feasibility and Safety of Intratympanic Administration of Sustained\u2010Exposure Dexamethasone Thermosensitive Gel (OTO\u2010104) for Prevention of Cisplatin\u2010Induced Hearing Loss in Children: A Multisite Phase 2 Randomized Clinical Trial"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5280-990X","authenticated-orcid":false,"given":"David R.","family":"Freyer","sequence":"first","affiliation":[{"name":"Cancer and Blood Disease Institute Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Departments of Pediatrics, Medicine, and Population and Public Health Sciences, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J. 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