Sodium thiosulfate may protect against cisplatin-induced hearing loss in paediatric cancer
Adding sodium thiosulfate to cisplatin chemotherapy regimen in children and adolescents with cancer reduced their likelihood of developing cisplatin-induced hearing loss, especially for children below 5 years of age, according to the randomized open-label phase III ACCL0431* study.
“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,” said Dr Eric Bouffet from The Hospital for Sick Children at University of Toronto in Ontario, Canada, in a separate commentary. [Lancet Oncol 2016;doi:10.1016/S1470-2045(16)30630-1]
Among 104 participants at 4 weeks post-treatment in combination with chemotherapy regimen, less patients from the sodium thiosulfate group developed hearing loss compared with the control (observation) group (28.6 percent vs 56.4 percent; p=0.00022). Sodium thiosulfate-treated patients were almost 70 percent less likely to develop hearing loss than controls, even after adjusting for stratification variables (odds ratio, 0.31, 95 percent confidence interval [CI], 0.13–0.73; p=0.0036). [Lancet Oncol 2016;doi:10.1016/S1470-2045(16)30625-8]
For patients younger than 5 years, the sodium thiosulfate group showed a substantially lower hearing loss incidence than the control group (21.4 percent vs 73.3 percent). In contrast, the between-group difference in hearing loss incidence was not as obvious for older patients (31.4 percent vs 50.0 percent).
Haematological toxicity was similar between the sodium thiosulfate vs control groups (77 percent vs 77 percent; p=0.95), with neutropenia being the most common grade 3–4 haematological adverse event (AE) reported in both groups (66 percent vs 65 percent).
For nonhaematological toxicity, aggregate nephrotoxicity was more common in sodium thiosulfate-treated patients than controls (25 percent vs 13 percent), with hypokalaemia being the most common nonhaematological AE (17 percent vs 12 percent).
“Nephrotoxicity ... was more common in the sodium thiosulfate group ... not because of an abnormal serum creatinine or glomerular filtration rate but rather, because of hypophosphataemia and hypokalaemia,” said the authors, although they had no explanation for this observation.
Of the 194 serious AEs reported in 26 participants in the sodium thiosulfate group, decreased neutrophil count was the most common (13 percent), followed by decreased platelet count (12 percent), and anaemia (11 percent), although none were seen as “probably or definitely related to sodium thiosulfate”, according to the researchers.
Among patients with localized disease, event-free survival or overall survival were not significantly different between groups. However, patients with disseminated disease who received sodium thiosulfate had significantly lower overall survival than those who did not (relative hazard ratio, 4.10; p=0.009) during a median follow-up period of 3.2–3.8 years.
According to the researchers, the tumour protective potential of sodium thiosulfate might be most pronounced in patients with poorer prognosis. The heterogeneity of the enrolled population comprising different tumour types could also contribute to the differences.
“The significantly lower overall survival seen in participants with disseminated disease ... necessitates caution when considering a future role for sodium thiosulfate,” said the authors, who anticipated further results from the ongoing SIOPEL-6** study, which is investigating the effect of sodium thiosulfate in children with hepatoblastoma.