On September 20, 2022, sodium thiosulfate was approved to reduce the risk of ototoxicity associated with cisplatin in pediatric patients (aged ≥ 1 month) with localized, nonmetastatic solid tumors.1
Supporting Efficacy Data
Approval was based on findings in the multicenter open-label SIOPEL 6 (ClinicalTrials.gov identifier NCT00652132) and COG ACCL0431 trials (NCT00716976).
In SIOPEL 6, a total of 114 patients with standard-risk hepatoblastoma were randomly assigned to receive six cycles of perioperative cisplatin-based chemotherapy with (n = 61) or without (n = 53) intravenous (IV) sodium thiosulfate administered at the recommended body weight–based doses. The primary outcome measure was grade ≥ 1 hearing loss on the Brock scale, assessed after treatment or at age ≥ 3.5 years. Hearing loss occurred in 39% vs 68% of patients with vs without sodium thiosulfate (unadjusted relative risk = 0.58, 95% confidence interval [CI] = 0.40–0.83).
OF NOTE
Sodium thiosulfate has warnings/precautions for hypersensitivity, hypernatremia and hypokalemia, and nausea and vomiting. It is contraindicated in patients with history of severe hypersensitivity to sodium thiosulfate or any of its components.
In COG ACCL0431, a total of 77 evaluable patients with solid tumors were randomly assigned to chemotherapy including cumulative cisplatin doses of at least 200 mg/m2 with individual doses infused over up to 6 hours with (n = 39) or without (n = 38) sodium thiosulfate at doses bioequivalent to the recommended dose. The primary outcome measure was hearing loss, based on American Speech-Language-Hearing Association criteria at 4 weeks after the final course of cisplatin. Hearing loss occurred in 44% vs 58% of patients with vs without sodium thiosulfate (unadjusted relative risk = 0.75, 95% CI = 0.48–1.18).
How It Is Used
The recommended doses are 10 g/m2, 15 g/m2, and 20 g/m2, according to a body weight of up to 5, 5 to 10, and more than 10 kg, respectively, via 15-minute IV infusion following cisplatin administration of 1 to 6 hours’ duration.
Safety Profile
In SIOPEL 6 or COG ACCL0431, the most common adverse events of any grade occurring in at least 25% of the sodium thiosulfate groups and at an incidence of at least 5% vs the cisplatin-alone groups were vomiting (85% vs 54%), nausea (40% vs 30%), decreased hemoglobin (34% vs 29%), hypernatremia (26% vs 4%), and hypokalemia (27% vs 20%). Grade 3 or 4 adverse events observed in at least 10% of the sodium thiosulfate groups and at an incidence of at least 5% vs the cisplatin-alone groups included hypokalemia (27% vs 20%), hypophosphatemia (20% vs 11%), stomatitis (14% vs 6%), and hyponatremia (12% vs 6%).
KEY POINTS
- Sodium thiosulfate was approved to reduce the risk of ototoxicity associated with cisplatin in pediatric patients (aged ≥ 1 month) with localized, nonmetastatic solid tumors.
- The recommended doses are 10 g/m2, 15 g/m2, and 20 g/m2, according to a body weight of < 5, 5 to 10, and > 10 kg, respectively, via 15-minute IV infusion following cisplatin administration of 1 to 6 hours’ duration.
Serious adverse events occurred in 40% of patients in the sodium thiosulfate group in SIOPEL 6 and in 36% in COG ACCL0431. Sodium thiosulfate was discontinued in one patient in each trial because of a grade 2 hypersensitivity reaction in both.
Sodium thiosulfate has warnings/precautions for hypersensitivity, hypernatremia and hypokalemia, and nausea and vomiting. It is contraindicated in patients with history of severe hypersensitivity to sodium thiosulfate or any of its components.
REFERENCE
1. Pedmark (sodium thiosulfate injection) for intravenous use prescribing information, Fennec Pharmaceuticals, Inc, September 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212937s000lbl.pdf. Accessed November 16, 2022.
