What is the appropriate use of sodium thiosulphate in the Van Driel protocol for ophthalmic conditions?

Sodium Thiosulfate in the Van Driel Protocol for Cisplatin-Induced Ototoxicity Prevention

Sodium thiosulfate should be administered as a 15-minute infusion at a dose of 16-20 g/m² starting 6 hours after completion of cisplatin infusion to prevent cisplatin-induced ototoxicity in patients receiving cisplatin chemotherapy. 1

Indications Based on Cancer Type

Non-metastatic Hepatoblastoma

• Strong recommendation for sodium thiosulfate administration in patients with non-metastatic hepatoblastoma 1
• High-quality evidence shows sodium thiosulfate provides effective otoprotection without reducing survival in this specific population 1

Other Non-metastatic Cancers

• Weak recommendation for sodium thiosulfate use in patients with non-metastatic cancers other than hepatoblastoma 1
• In the ACCL0431 trial, 3-year event-free survival was 60% with sodium thiosulfate versus 66% without it (p=0.73), and 3-year overall survival was 83% with sodium thiosulfate versus 89% without it (p=0.88) 1
• The evidence quality is considered low due to post-hoc classification of disease status and potential for confounding 1

Metastatic Cancers

• Weak recommendation against routine use of sodium thiosulfate in patients with metastatic cancers 1
• In patients with metastatic cancers in the ACCL0431 trial, 3-year overall survival was significantly lower with sodium thiosulfate (45% vs 84%, p=0.009) 1
• Discussion with patients and families is important as some may still choose this option when balancing hearing preservation against potential survival concerns 1

Administration Protocol

• Sodium thiosulfate should be administered as a 15-minute infusion starting 6 hours after completion of cisplatin infusion 1
• Either 16 g/m² (used in SIOPEL 6) or 20 g/m² (used in ACCL0431) dosing is acceptable 1
• The cisplatin infusion duration should be 6 hours or less to accommodate the timing of sodium thiosulfate administration 1
• Do not alter cisplatin infusion duration solely to reduce ototoxicity 1

Important Considerations and Caveats

• The efficacy of sodium thiosulfate in preventing further hearing deterioration in patients who have already developed cisplatin-induced ototoxicity or have pre-existing hearing loss is unknown 1
• The recommendation strength varies based on cancer type and metastatic status due to concerns about potential negative effects on survival in certain populations 1
• Patient representatives have advocated for discussing sodium thiosulfate as an option with patients and families, particularly in cases where hearing preservation may significantly impact quality of life 1
• There may be clinical scenarios where the benefits of sodium thiosulfate administration likely outweigh the risks, such as in a child with blindness 1

Alternative Otoprotective Approaches Not Recommended

• Strong recommendation against using amifostine for prevention of cisplatin-induced ototoxicity 1
• Strong recommendation against using sodium diethyldithiocarbamate 1
• Strong recommendation against using intratympanic middle ear therapy 1

Research Gaps

• More research is needed to confirm the efficacy and safety of sodium thiosulfate in non-metastatic cancers other than hepatoblastoma 1
• Further studies are required to determine the optimal sodium thiosulfate dosing for pediatric patients 1
• Additional research is needed to evaluate the safety of sodium thiosulfate in patients with metastatic cancers 1
• Studies focusing on patients with pre-existing hearing loss or who have already developed some degree of cisplatin-induced ototoxicity are lacking 1