Sodium thiosulfate otoprotective in cisplatin-treated pediatric cancer patients
medwireNews: Treatment with the antioxidant sodium thiosulfate can reduce the incidence of platinum-induced hearing loss in children and adolescents with cancer treated with cisplatin, research suggests.
“This benefit seems to be greatest in children younger than 5 years, who are most susceptible to cisplatin-induced hearing loss,” David Freyer (Children’s Hospital Los Angeles, California, USA) and team observe in The Lancet Oncology.
They urge caution, however, as their post hoc analysis revealed significantly lower overall survival (OS) among participants with disseminated disease who received sodium thiosulfate relative to those in the control observation group.
The phase III ACCL0431 trial included 104 children aged 1–18 years with a new diagnosis of any malignancy routinely treated with cisplatin. Participants were required to have normal audiometry at baseline, with 49 randomly allocated to receive the antioxidant and 55 to undergo observation.
Sodium thiosulfate 16 g/m2 per day, administered 6 hours after completion of the cisplatin dose, significantly reduced the incidence of hearing impairment (as assessed by the American Speech-Language-Hearing Association criteria) 4 weeks after the final cisplatin dose relative to observation, at 28.6% versus 56.4%.
Among participants under 5 years of age, the between-group difference was even more marked, with 21.4% of sodium thiosulfate-treated children experiencing hearing loss at this timepoint compared with 73.3% of those in the observation group.
“The potential clinical effect of these findings is to offer, at a very affordable cost, a possible decrease in a toxicity that has too often been regarded as a price to pay for survival, especially for patients with germ cell tumours, hepatoblastoma, neuroblastoma, osteosarcoma, and medulloblastoma, in which cisplatin is part of the standard of care,” Eric Bouffet (The Hospital for Sick Children, Toronto, Ontario, Canada) writes in an accompanying commentary.
However, he also finds the survival difference between the sodium thiosulfate and control groups in patients with disseminated disease “troubling.”
Specifically, among these children, those treated with sodium thiosulfate had a significant 4.10-fold increased risk for death relative to those who underwent observation, with corresponding 3-year OS rates of 45% and 84%. By contrast, event-free survival was comparable between treatment arms.
And both overall and event-free survival did not differ significantly between participants given and not given sodium thiosulfate among those with localized disease.
Bouffet says that the results “might trigger some concerns and negatively affect the introduction of sodium thiosulfate in protocols for high-risk patients.”
But he adds: “In the absence of a clear understanding of the underlying determinants of the difference in the outcomes reported, we can only recommend caution and hope that this finding will not prevent the development of prevention of cisplatin-induced hearing loss protocols in this population.”
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