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Sodium thiosulfate lowers risk for hearing loss among children with hepatoblastoma
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Children with standard-risk hepatoblastoma who received sodium thiosulfate 6 hours after cisplatin chemotherapy had a 48% lower incidence of cisplatin-induced hearing loss, according to phase 3 results from the SIOPEL 6 clinical trial published in The New England Journal of Medicine.
“After 30 years of studying the side effects of cisplatin chemotherapy in children, it is wonderful to find an agent that can significantly reduce the incidence of hearing loss in children without impacting survival,” Penelope (Peppy) Brock, MD, PhD, MA, consultant pediatric oncologist at Great Ormond Street Hospital for Children NHS Foundation Trust in London told HemOnc Today. “I long to see children cured of their cancer, free to hear, to grow up enjoying normal lives, reaching their full potential, [and] free to forget they ever had cancer.”
Cisplatin chemotherapy and surgery are standard treatments for children with standard-risk hepatoblastoma. However, hearing loss — a side effect of cisplatin chemotherapy — can affect learning, development and quality of life among young children.
“No child should have to face the cost of cure as being lifelong hearing loss and disability,” Brock said.
Previous studies have shown that sodium thiosulfate may have an otoprotective effect, with maximum efficacy when administered 4 to 8 hours after cisplatin therapy.
Researchers of this international, cooperative, prospective, randomized trial addressed whether delayed administration of sodium thiosulfate would reduce incidence and severity of hearing loss caused by cisplatin chemotherapy without impacting OS and EFS.
Researchers randomly assigned children aged 1 month to 18 years to receive 80 mg/m2 cisplatin alone over 6 hours (n = 52; median age, 13.4 months) or cisplatin plus 20 g/m2 IV sodium thiosulfate (n = 57; median age, 12.8 months) over a 15-minute period, 6 hours after discontinuing cisplatin in four preoperative and two postoperative courses.
Investigators used the Brock grade scale to measure hearing loss.
Absolute hearing threshold at a minimum age of 3.5 years measured by pure-tone audiometry served as the primary endpoint. Secondary endpoints included OS and EFS at 3 years.
The intention-to-treat population comprised 109 children, of whom 101 could be evaluated for the primary endpoint.
Hearing loss of grade 1 or higher occurred among 18 of 55 children (33%; 95% CI, 21-47) evaluated in the cisplatin-sodium thiosulfate group compared with 29 of 46 children (63%; 95% CI, 48-77) in the cisplatin alone group.
The RR of any hearing loss with sodium thiosulfate was 0.52 (95% CI, 0.33-0.81), which indicated a 48% lower risk than with cisplatin alone.
At median 52 months of follow-up, 3-year OS was 98% (95% CI, 88-100) in the cisplatin-sodium thiosulfate group and 92% (95% CI, 81-97) in the cisplatin-alone group.
The 3-year EFS rates were 82% (95% CI, 69-90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65-88) in the cisplatin alone group.
Progressive disease developed in the same number of children in each group.
Researchers observed a total 68 serious adverse events — 16 serious adverse reactions — among both groups. Eight of the serious adverse reactions were deemed as possibly, probably or definitely related to sodium thiosulfate. These included grade 3 infections in two children, grade 3 neutropenia in two children, grade 3 anemia leading to transfusion in one child and tumor progression in two children.
One child experienced grade 2 nausea and vomiting and discontinued sodium thiosulfate treatment after cycle two.
“Even though some of the limitations of hearing loss can be reduced in the resource-rich world, life is not the same as it would be free from intervention. In resource-challenged nations, life without normal hearing, development and social interaction means risking a life of dependency,” Brock said. “I long to see this drug widely distributed throughout the resource-challenged nations as well as the resource-rich nations.” – by Melinda Stevens
For more information:
Penelope (Peppy) Brock, MD, PhD, MA, can be reached at Badgers, 26 Estridge Way, Tonbridge, TN10 4JT, United Kingdom; email: peppybrock@gmail.com.
Disclosures: Brock reports no relevant financial disclosures. Please see the study for a list of all other researchers’ relevant financial disclosures.
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