Antioxidant Reduced Hearing Loss in Cisplatin-Treated Pediatric Cancers

The antioxidant sodium thiosulfate protects children and adolescents against cisplatin-induced hearing loss without any added serious adverse effects, according to a randomized study.

More than 2,000 children between the ages of 1 and 15 receive cisplatin each year in the United States. “Unfortunately, cisplatin causes clinically significant cisplatin-induced hearing loss, which is characterized as progressive, irreversible, bilateral, and often accompanied by tinnitus,” wrote study authors led by David R. Freyer, DO, of Children’s Hospital Los Angeles. The hearing loss occurs as a result of progressive death of cochlear outer hair cells.

Earlier research has suggested that sodium thiosulfate might protect against this effect of cisplatin. In the new study, 125 children and adolescents with newly diagnosed cancer and normal hearing were randomized to receive either sodium thiosulfate (6 hours after each cisplatin dose) or observation along with cisplatin-based chemotherapy; a total of 104 patients (49 in the sodium thiosulfate group, 55 control patients) were assessable for the primary endpoint. The results were published online ahead of print in Lancet Oncology.

Most patients were male, and most were white; germ cell tumors, medulloblastoma, osteosarcomas, and others were among the tumors included. Most patients had localized disease.

In total, 14 patients on sodium thiosulfate had hearing loss at 4 weeks after the final cisplatin dose, compared with 31 patients in the control group (P = .00022). An adjusted analysis showed an odds ratio for developing hearing loss with sodium thiosulfate of 0.31 (95% CI, 0.13–0.73; P = .0036).

The difference was especially pronounced among patients younger than 5 years old. Of 14 such patients receiving sodium thiosulfate, only 3 experienced hearing loss, compared with 11 of 15 in the control group. The difference was not as substantial among older patients. Excluding 8 patients who underwent cranial irradiation still yielded significantly lower likelihood of hearing loss with sodium thiosulfate.

Sixty-seven of the patients were also assessable for hearing loss after 1 year. At that point, 9 of 32 who received sodium thiosulfate (28%) had hearing loss, compared with 19 of 35 (54%) control patients (P = .0015). Overall and event-free survival did not differ between the groups.

The use of sodium thiosulfate did not appear to add substantial excess toxicity. Grade 3/4 neutropenia occurred in 66% of participant cycles in the intervention group, compared with 65% of those in the control group. The most common grade 3/4 non-hematological adverse event was hypokalemia, which occurred in 17% of cycles in the sodium thiosulfate group and in 12% in the control group. None of the serious adverse events that occurred were deemed probably or definitely related to sodium thiosulfate.

“This study addresses a clinically important goal because of the profound, negative effect of ototoxicity on quality of life for survivors of cancer treated during young childhood and adolescence,” the authors wrote. “It is reasonable to assume the benefits of preventing cisplatin-induced hearing loss and chronic tinnitus include reduction of their many downstream effects on language acquisition, learning, psychosocial development, and social functioning.”