Sodium thiosulfate may confer otoprotection in children undergoing cisplatin therapy
Administering sodium thiosulfate 6 hours after cisplatin therapy almost halved the incidence of hearing loss in children with hepatoblastoma, according to results of the phase III SIOPEL 6* trial.
“[T]he addition of delayed sodium thiosulfate to cisplatin led to a 48 percent lower risk of hearing loss … without jeopardizing overall or event-free survival,” said the researchers.
The trial, conducted in 12 countries, involved 109 children aged >1 month to <18 years with treatment-naïve, standard-risk hepatoblastoma** who were randomized to receive six courses (four preoperative and two postoperative) of intravenous cisplatin (80 mg/m2 administered over 6 hours; n=52) alone or in addition to sodium thiosulfate (20 g/m2 administered over 15 minutes 6 hours after completing cisplatin infusion; n=57). Absolute hearing threshold, measured using pure-tone audiometry, was done at age ≥3.5 years.
Incidence of grade ≥1 hearing loss was almost halved in children who received sodium thiosulfate after cisplatin compared with those who received cisplatin only (33 percent vs 63 percent, relative risk, 0.52, 95 percent confidence interval, 0.33–0.81; p=0.002). [N Engl J Med 2018;378:2376-2385]
After a median follow-up of 52 months, 3-year overall survival was 98 percent among children who received cisplatin + sodium thiosulfate compared with 92 percent of children who received cisplatin only, while event-free survival was 82 and 79 percent, respectively.
“There was no significant difference in the rates of event-free survival or overall survival between the two groups,” said the researchers. “The initiation of sodium thiosulfate after a 6-hour delay from the completion of cisplatin administration caused no tumour protection and did not adversely affect disease outcome.”
Sixty-eight serious adverse events were reported, with one incidence of metabolic acidosis deemed by researchers to be related to sodium thiosulfate. Of the 16 serious adverse reactions reported, eight were thought to be at least possibly related to sodium thiosulfate, including grade 3 infections (n=2), grade 3 neutropenia (n=2), grade 3 anaemia requiring transfusion (n=1), and tumour progression (n=2). Despite the use of prophylactic anti-emetics, patients on sodium thiosulfate frequently experienced nausea and vomiting.
“The combination of cisplatin monotherapy and surgery is the standard of care for children with standard-risk disease and results in good long-term survival,” said the researchers. [N Engl J Med 2009;361:1662-1670]
“We’re lucky to have such an effective treatment for this type of liver cancer. But like many cancer treatments, there can also be long-term side effects. For children treated with cisplatin alone, a huge proportion are left with permanent hearing loss, which can be utterly debilitating. Even mild hearing loss can severely impact a child’s future development. Key consonants [like ‘s’, ‘h’, and ‘f’] are heard at high frequencies, and their loss can be particularly difficult for children who haven’t yet developed speech,” said study lead author Dr Penelope Brock from Great Ormond Street Hospital, London, UK.
“This treatment combination could help ensure that parents aren’t faced with an upsetting scenario where successful cancer treatment comes at the cost of their child’s hearing,” she said.
“[W]e’re delighted to see that we can safeguard the future development of more children, without compromising the chance of curing their cancer,” added Professor Pam Kearns from the University of Birmingham in Birmingham, UK, who was not affiliated with the study.