Sodium Thiosulfate Protocol as per OVIHIPEC Trial
The recommended sodium thiosulfate (STS) protocol based on the OVIHIPEC trial is to administer STS as a 15-minute infusion at a dose of 20 g/m² starting 6 hours after completion of cisplatin infusion, with the cisplatin infusion duration being 6 hours or less. 1, 2
Administration Protocol Details
- STS should be administered as a 15-minute intravenous infusion starting exactly 6 hours after the completion of each cisplatin dose 1, 2
- The recommended dose is 20 g/m² as used in the SIOPEL 6 trial, although 16 g/m² as used in the ACCL0431 trial is also considered acceptable 2, 3
- The cisplatin infusion must be 6 hours or less in duration to accommodate the timing of STS administration 1, 2
- This protocol should be followed for each cycle of cisplatin chemotherapy 3
Evidence Base and Efficacy
- The STS protocol was established based on two key randomized controlled trials: SIOPEL 6 and ACCL0431 1
- In SIOPEL 6, STS reduced hearing loss incidence from 63% to 33% in children with standard-risk hepatoblastoma (p=0.002) 3
- The protective effect was achieved without compromising survival outcomes - 3-year event-free survival was 82% with STS versus 79% without STS 1, 3
- STS works by interacting directly with cisplatin to produce inactive platinum species and by increasing intracellular antioxidant levels 4
Clinical Indications
- Strong recommendation for STS use in patients with non-metastatic hepatoblastoma 1, 2
- Weak recommendation for STS use in patients with non-metastatic cancers other than hepatoblastoma 1, 2
- Weak recommendation against routine STS use in patients with metastatic cancers due to potential concerns about reduced efficacy 2
Important Considerations and Caveats
- The efficacy of STS in preventing further hearing deterioration in patients who have already developed cisplatin-induced ototoxicity or have pre-existing hearing loss remains unknown 1, 2
- STS has shown few high-grade toxic effects in clinical trials 3
- STS has demonstrated nephroprotective effects in addition to its otoprotective properties, which may be an additional benefit when using cisplatin 5
- The protocol is most applicable to patients receiving multiple cycles of cisplatin (six cycles in SIOPEL 6), and the strong recommendation might not apply to patients receiving fewer cycles 1
Alternative Approaches
- Strong recommendations exist against using alternative agents such as amifostine, sodium diethyldithiocarbamate, and intratympanic middle ear therapy for prevention of cisplatin-induced ototoxicity 2
- STS has demonstrated superior otoprotective effects compared to other agents such as diethyldithiocarbamate, WR-2721, and fosfomycin in preclinical studies 6