From the Guidelines
Sodium thiosulfate is the preferred cytoprotective agent for preventing cisplatin-induced ototoxicity in children and adolescents with cancer, particularly those with non-metastatic hepatoblastoma, due to its proven efficacy and safety profile, as evidenced by high-quality studies 1.
Key Points
- Sodium thiosulfate has been shown to significantly reduce the risk of cisplatin-induced ototoxicity in pediatric patients, with a risk ratio of 0.51 (95% CI 0.37-0.71) compared to no treatment 1.
- The recommended dose of sodium thiosulfate is 16 g/m² or 20 g/m², administered 6 hours after cisplatin to avoid interference with antitumor activity 1.
- Amifostine, on the other hand, has not been shown to be effective in preventing cisplatin-induced ototoxicity in children and adolescents with cancer, and its use is not recommended for this purpose 1.
- The choice between sodium thiosulfate and amifostine depends on the specific toxicity concern, patient population, and tumor type being treated, with sodium thiosulfate being the preferred agent for ototoxicity prevention in pediatric patients.
Mechanism of Action
- Sodium thiosulfate works by binding to cisplatin metabolites, preventing their interaction with cochlear cells, while amifostine is a prodrug activated by alkaline phosphatase to form free thiol compounds that scavenge reactive cisplatin species.
Clinical Implications
- The use of sodium thiosulfate for ototoxicity prevention in pediatric patients with cancer can help improve their quality of life and reduce the risk of long-term hearing loss.
- Clinicians should consider the timing of administration and the specific dose of sodium thiosulfate to balance cytoprotection with maintaining cisplatin's anticancer efficacy.
From the Research
Comparison of Sodium Thiosulfate and Amifostine for Cisplatin Cytoprotection
- Amifostine has been shown to be effective in reducing the incidence of cumulative nephrotoxicity from cisplatin in several studies 2, 3.
- The mechanism of amifostine's protective effect is thought to be associated with the suppression of Fas/FasL expression in renal tissues 4.
- Amifostine has been investigated extensively and appears particularly effective with cisplatin and cyclophosphamide, which operate via direct binding to the active species of these alkylating agents 5.
- There is no direct comparison between sodium thiosulfate and amifostine for cisplatin cytoprotection in the provided studies.
- However, amifostine has been shown to be effective in reducing nephrotoxicity, neurotoxicity, and hematological toxicity associated with cisplatin treatment 2, 3.
- The use of amifostine as a cytoprotective agent has been supported by several studies, which demonstrate its ability to reduce morbidity in cancer patients receiving radiation and chemotherapy without compromising the antineoplastic activity of the cancer therapies employed 2, 3, 5.
- Other studies have also demonstrated the protective effects of amifostine in other tumor types and other chemotherapy, radiation, and radiochemotherapy regimens 2, 3.
Key Findings
- Amifostine reduces the incidence of cumulative nephrotoxicity from cisplatin 3.
- Amifostine protects against nephrotoxicity induced by both single and repeated doses of cisplatin without affecting the antitumor effects of cisplatin 3.
- Amifostine has been shown to stimulate hematopoietic stem cells and has been investigated as a therapy for patients with myelodysplastic syndrome 2.
- Amifostine is generally well tolerated, with adverse effects that are usually reversible and manageable 2.
Mechanism of Action
- The mechanism of amifostine's protective effect is thought to be associated with the suppression of Fas/FasL expression in renal tissues 4.
- Amifostine protects a broad range of normal tissues from the toxic effects of chemotherapy and radiotherapy without attenuating tumor response 2.
- The selective protection of amifostine is due to the greater conversion and uptake of the active metabolite, WR-1065, in normal versus neoplastic tissues 2.