In a phase III International Liver Tumor Strategy Group trial (SIOPEL 6) reported in The New England Journal of Medicine, Brock et al found that sodium thiosulfate reduced cisplatin-induced hearing loss in pediatric patients with standard-risk hepatoblastoma.
The trial enrolled a total of 116 children aged > 1 month to < 18 years from 52 centers in 12 countries between 2007 and 2014. Of these, 109 eligible patients constituted the intention-to-treat population and 101 could be evaluated for the primary endpoint. Standard-risk hepatoblastoma was defined as ≤ 3 involved liver sectors, no metastatic disease, and alpha-fetoprotein level of > 100 ng/mL. Patints were randomized to receive cisplatin alone at 80 mg/m2 over 6 hours (n = 52; median age = 13.4 years) or cisplatin plus sodium thiosulfate at 20 g/m2 given intravenously for 15 minutes 6 hours after discontinuation of cisplatin (n = 57; median age = 12.8 years) for four preoperative and two postoperative courses.
The primary endpoint was the absolute hearing threshold measured by pure-tone audiometry at a minimum age of 3.5 years. Hearing loss was assessed by Brock grade, with higher grades on a scale of 0 to 4 indicating greater hearing loss. The main secondary endpoints were overall survival and event-free survival at 3 years.
Audiometry and Survival Outcomes
Final audiometry was performed at a median of 3 years after randomization. Hearing loss of grade ≥ 1 occurred in 18 (33%) of 55 children in the cisplatin-sodium thiosulfate group vs 29 (63%) of 46 in the cisplatin-alone group (relative risk = 0.52, P = .002).
At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% in the cisplatin-sodium thiosulfate group vs 79% in the cisplatin group, and 3-year rates of overall survival were 98% vs 92%.
Grade 3 or 4 adverse events occurring in ≥ 10% of the cisplatin-sodium thiosulfate group or the cisplatin group were grade 3 infection (23% vs 31%), anemia (20% vs 15%), neutropenia (17% vs 12%), grade 3 febrile neutropenia (14% vs 19%), and elevated liver enzymes (7% vs 12%).
The investigators concluded, “The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival.”
The study was funded by Cancer Research UK and others.
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