Sodium Thiosulfate May Offer Ototoxicity Protection During Platinum Chemotherapy

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Sodium thiosulfate (STS) is protective against ototoxicity in patients undergoing platinum-based chemotherapy without adversely impacting treatment efficacy, suggest the results of a systematic review and meta-analysis. 

Yen-Fu Cheng, from Taipei Veterans General Hospital in Taipei City, Taiwan, and co-workers identified three randomised clinical trials and one controlled study of STS treatment in 278 patients undergoing platinum-based chemotherapy for hepatoblastoma, central nervous system malignancies, head and neck cancers and other tumour types. 

Two studies assessed the use of intravenous STS given 6 hours after cisplatin infusion as either a single dose of 16 or 20 g/m2, while a third study tested a two-dose strategy, with the first 20 g/m2 dose administered 2 or 4 hours after carboplatin infusion and a second 16 g/m2 dose given at 6 or 8 hours. The fourth study assessed an STS transtympanic injection after cisplatin, given as a 0.1 mL dose of a 0.5 M gel. 

Ototoxicity was defined in three studies using the American Speech–Language–Hearing Association criteria (>20 dB decrease in one test frequency or >10 dB decrease at two test frequencies), while the fourth used the Brock grading system for hearing levels. 

Yen-Fu Cheng and team report that the 158 patients given STS had a significantly reduced likelihood of ototoxicity during the course of chemotherapy versus those who did not receive the treatment, with a relative risk (RR) of 0.61. 

Pooled analysis of the three trials assessing intravenous STS also indicated that treatment was associated with a significant reduction in ototoxicity compared with no STS (RR=0.57), but the fourth trial testing transtympanic delivery in head and neck cancer patients achieved only a nonsignificant reduction in risk (RR=0.89). 

“Various factors may attenuate the association of STS with otoprotective outcomes by transtympanic delivery”, Yen-Fu Cheng and team postulate, such as the permeability of the solution or the passage of the gel through middle ear effusions. 

Two studies assessed haematopoietic outcomes and did not find a link between STS treatment and an increased risk of neutropenia, thrombocytopenia or anaemia. 

The researchers hypothesised that the covalent bonding of STS to cisplatin may attenuate the chemotherapy agent’s anticancer activity as well as reducing ototoxicity, but pooled analysis did not indicate that receipt of STS therapy was associated with a significant reduction in event-free survival or overall survival. 

Sensitivity analyses confirmed that STS use was associated with reduced ototoxicity even when excluding the non-randomised controlled trial, the trial that included carboplatin chemotherapy, the study using the Brock grading system, or the study with a small number of patients.  

But the investigators emphasize that the small number of included trials and differences in participants by age, race or ethnicity, and tumour type may also “contribute to bias”. 

The authors conclude in JAMA Network Open that “further large-scale studies are essential to provide more detailed information and convincing results”, especially to ascertain whether survival outcomes are affected by STS therapy. 

Reference 

Chen C-H, Huang C-Y, Lin H-YH; et al. Association of sodium thiosulfate with risk of ototoxic effects from platinum-based chemotherapy. A systematic review and meta-analysis. JAMA Netw Open 2021;4(8):e21187895. doi:10.1001/jamanetworkopen.2021.18895