Cisplatin is an effective treatment of childhood hepatoblastoma, but can cause severe and permanent ototoxicity; in paediatric patients, even minor hearing loss can drastically affect learning, development, and quality of life (QOL). Now, results of the randomized, phase III SIOPEL 6 trial demonstrate that sodium thiosulfate (STS) has considerable efficacy in preventing cisplatin-induced hearing loss.
In SIOPEL 6, 109 children with standard-risk hepatoblastoma received 4 preoperative and 2 postoperative cycles of cisplatin (80 g/m2), with 57 patients also receiving STS at 20 g/m2 intravenously 6 h after cisplatin administration. Delayed administration of STS was chosen on the basis of preclinical and clinical evidence in order to maximize the otoprotective effect while minimizing potential tumour-protective effects.
“The most significant finding of this study is that it confirms that delayed treatment with STS protects the majority of children from lifelong cisplatin-induced hearing loss,” states lead author Penelope Brock. Hearing loss of any grade (according to the Brock 4-point scale) occurred in 33% of patients who received STS versus 63% of those treated with cisplatin alone — a relative risk reduction of 48% (P = 0.002). Moreover, 3-year event-free survival (82% versus 79%) and overall survival (98% versus 92%) were similar in the STS and cisplatin-only groups.
“This study should dispel the fears of delayed STS tumour protection, raised by a post-hoc analysis of the ACCL0431 trial,” says Brock. “Notably, this drug could most profoundly improve the QOL of patients in the developing world, where cisplatin is extensively used but the devastating personal, educational, and social consequences of hearing loss often remain unaddressed,” she adds, concluding, “ultimately, STS could be made available to all adults and children receiving cisplatin chemotherapy.”
Brock, P. R. et al. Sodium thiosulfate for protection from cisplatin-induced hearing loss. N. Engl. J. Med. 378, 2376–2385 (2018)
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Killock, D. Sodium thiosulfate halves the risk of cisplatin-induced hearing loss. Nat Rev Clin Oncol 15, 533 (2018). https://doi.org/10.1038/s41571-018-0067-2