Chemotherapy-induced hearing loss reduced in children by a new treatment

A Phase III trial involving 38 participating Children’s Oncology Group hospitals in the USA and Canada has demonstrated that treatment with sodium thiosulfate significantly reduced the incidence of hearing loss induced by cisplatin.

These findings, published recently in Lancet Oncology, suggest that sodium thiosulfate could improve the quality of life of children and adolescents undergoing chemotherapy.

Cisplatin is a widely used chemotherapeutic agent and is effective against a number of cancers. However, the drug is associated with adverse side effects; for example, it can cause permanent hearing loss and tinnitus. This side effect can be particularly detrimental in young children as hearing loss could result in impaired language development and difficulty learning.

The study, termed ACCL0431, enrolled 125 children and adolescents with newly-diagnosed cancer over a 4-year period, all 1–18 years of age. The children were randomly assigned to either receive sodium thiosulfate or observation in addition to their planned chemotherapy regime.

Individuals in the therapy group were given 16 g / m2 of sodium thiosulfate intravenously 6 hours after each cisplatin dose. In addition, the team assessed each participants hearing using standard audiometry.

The researchers observed that there was a significantly reduced incidence of cisplatin-induced hearing loss in those treated with sodium thiosulfate; 14 individuals suffered hearing loss in the therapy group compared with 31 in the control group. The greatest benefit was seen in children < 5 years of age, who are most susceptible to cisplatin-induced hearing loss.

The team also observed that sodium thiosulfate was well tolerated by participants and there were no incidences of serious adverse events linked to the treatment. Moreover, sodium thiosulfate had no effect on cancer survival in those with localized tumors, although survival appeared to be lower in those with metastatic disease who received sodium thiosulfate.

Preclinical and animal studies have previously reported the benefits of sodium thiosulfate; however, there are currently no proven treatments for preventing cisplatin-induced hearing loss whilst maintaining chemotherapeutic efficacy. This study is the first to demonstrate the effectiveness of sodium thiosulfate in children and additional research could further elucidate the benefits in specific subsets of cisplatin-treated patients.

Lead author and chair of the study David Freyer (Children’s Hospital Los Angeles, CA, USA) concluded: “This federally-funded, cooperative group study is the first to show that cisplatin-induced hearing loss can be reduced by about half in children and adolescents being treated for cancer. It is an important step toward developing a safe and effective strategy that will greatly improve quality of life for cancer survivors.”

Sources: 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. doi:10.1016/S1470-2045(16)30625-8 (2016) (Epub ahead of print);