Panizza Benedict J, O'Leary Stephen John, Hart Christopher David, Diwakarla Chandra Sai, Barnett Catherine, Lapuerta Pablo, Lee John, Raines Shane, Quigley Tera, Wolff Heather M, Keilty John, Ladwa Rahul, Porceddu Sandro V, McGrath Margaret, Seetharamu Nagashree, Fua Tsien, Rischin Danny
Princess Alexandra Hospital, Brisbane, Australia.
University of Queensland, Brisbane, Australia.
J Clin Oncol. 2025 Jul;43(19):2155-2163. doi: 10.1200/JCO.24.00905. Epub 2025 May 22.
This study evaluated DB-020, a formulation of thiosulfate for intratympanic (IT) injection, in patients receiving high-dose cisplatin chemotherapy.
This randomized phase Ib clinical trial enrolled patients older than 18 years from five centers in Australia and the United States scheduled for at least three cycles of cisplatin and total cumulative exposure of ≥280 mg/m. Patients received IT DB-020 (at a dose level of either 12% or 25%) in one ear and placebo in the other, once every 3 or 4 weeks, within 3 hours before receiving cisplatin. The primary end points were safety and tolerability, and the secondary end points included ototoxicity measured by air conduction audiometry. Ototoxicity was defined by American Speech-Language-Hearing Association criteria.
Twenty-two patients with a median age of 55.1 years were randomly assigned and received a mean total cumulative cisplatin dose of 255 mg/m. Mean number of cisplatin cycles was 2.3. Twenty patients had both baseline and follow-up audiometry. Ear pain of short duration was common after IT injection. There were no persistent tympanic perforations and no serious adverse events in the category of ear and labyrinth disorders. A progressive reduction in patient numbers was observed at each cycle due to patients ceasing cisplatin treatment. DB-020 treatment did not affect plasma thiosulfate concentrations. Ototoxicity after cisplatin administration was significantly more common in placebo-treated ears than in DB-020-treated ears (DB-020 placebo, = .0027). The incidence of ototoxicity (250-8,000 Hz) was 85.0% in placebo-treated ears, and 54.5% and 22.2% in ears treated with DB-020 12% and DB-020 25%, respectively.
DB-020 IT injections were tolerated by patients and showed meaningful reductions in cisplatin ototoxicity.
本研究评估了用于鼓室内（IT）注射的硫代硫酸盐制剂DB - 020在接受高剂量顺铂化疗患者中的效果。
这项随机1b期临床试验纳入了来自澳大利亚和美国五个中心的18岁以上患者，这些患者计划接受至少三个周期的顺铂化疗且总累积暴露量≥280mg/m²。患者在接受顺铂治疗前3小时内，每3或4周一次，一只耳接受IT DB - 020（剂量水平为12%或25%），另一只耳接受安慰剂。主要终点是安全性和耐受性，次要终点包括通过气导听力测定法测量的耳毒性。耳毒性根据美国言语 - 语言 - 听力协会标准定义。
22名中位年龄为55.1岁的患者被随机分配，平均顺铂总累积剂量为255mg/m²。顺铂周期的平均次数为2.3次。20名患者进行了基线和随访听力测定。IT注射后短时间的耳痛很常见。没有持续性鼓膜穿孔，也没有耳和迷路疾病类别的严重不良事件。由于患者停止顺铂治疗，每个周期观察到患者数量逐渐减少。DB - 020治疗不影响血浆硫代硫酸盐浓度。顺铂给药后的耳毒性在安慰剂治疗的耳朵中比在DB - 020治疗的耳朵中明显更常见（DB - 020 vs安慰剂，P = 0.0027）。安慰剂治疗耳朵的耳毒性（250 - 8000Hz）发生率为85.0%，12% DB - 020和25% DB - 020治疗的耳朵中分别为54.5%和22.2%。
患者对DB - 020鼓室内注射耐受，并且顺铂耳毒性有显著降低。
