TO THE EDITOR: Brock and colleagues (June 21 issue)1 report the results of International Liver Tumor Strategy Group (SIOPEL) 6, a randomized, controlled trial of sodium thiosulfate for protection from cisplatin-induced hearing loss. In addition to confirming the efficacy of sodium thiosulfate, as previously reported in the Children’s Oncology Group ACCL0431 trial,2 SIOPEL 6 provides compelling evidence that sodium thiosulfate did not compromise survival in its homogeneous population of children with standard-risk hepatoblastoma. In the drawing of conclusions for clinical practice, these results should be interpreted in combination with those of ACCL0431. The ACCL0431 design included multiple cancer types at any stage; a post hoc analysis showed that although survival in the sodium thiosulfate group was equivalent to that in the control group among patients with localized disease, it was significantly lower among those with disseminated disease (relative hazard ratio for death, 4.10; 95% confidence interval, 1.30 to 12.97; P = 0.009 by log-rank test). There was no clear explanation for this disparity.
Taken together, these trials provide definitive evidence that sodium thiosulfate reduces the incidence of cisplatin-induced hearing loss and suggest that sodium thiosulfate is safe to use in patients with standard-risk hepatoblastoma and probably in those with other localized cancers. However, the use of sodium thiosulfate in patients with disseminated disease may affect survival, and caution is warranted in that context.
Footnotes
Dr. Freyer reports being a scientific advisor for Otonomy and Sensorion, and Dr. Frazier being on the clinical advisory board of Decibel Therapeutics. No other potential conflict of interest relevant to this letter was reported.
Contributor Information
David R. Freyer, Children’s Hospital Los Angeles, Los Angeles, CA
A. Lindsay Frazier, Dana–Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA
Lillian Sung, Hospital for Sick Children, Toronto, ON, Canada
References
- 1.Brock PR, Maibach R, Childs M, et al. Sodium thiosulfate for protection from cisplatin-induced hearing loss. N Engl J Med 2018; 378: 2376–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Freyer DR, Chen L, Krailo MD, et al. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2017; 18:6 3–74. [DOI] [PMC free article] [PubMed] [Google Scholar]