Table 3.
Representative Emerging Otoprotectants for Use With Platinum-Based Chemotherapy
| Agent | Route | Mechanism | Comment |
|---|---|---|---|
| STS | IV | Thiol-reducing agent | In rats, STS protects against ototoxicity14 without reducing antitumor efficacy.101 Currently in phase III trials. Possible approaches include delayed administration, 14,87,100 two-compartment models, 4,5,104 and cochlear application.85,96 |
| Amifostine | IV | Metabolized to WR-1065, a thiol-reducing agent | Most trials show no otoprotection; dose intensity may be critical; routine use of amifostine to prevent platinum-associated neurotoxicity or ototoxicity is not currently supported by the American Society of Clinical Oncology 2008 Clinical Practice Guideline.105 |
| NAC | IV | Thiol-reducing agent | High dose (1,000 mg/kg) IV or intra-arterial NAC protects against cisplatin ototoxicity in the rat when given either 30 minutes prior to or 4 hours after chemotherapy and also blocks kidney toxicity and weight loss.14,78 Delayed IV NAC does not block chemotherapy antitumor efficacy.101 |
| d-methionine | PO, IV, or delivery to the round window | Glutathione modulator, free-radical scavenger | Animal studies have confirmed d-methionine protection from carboplatin- and cisplatin-induced ototoxicity.99 Effective delivered PO,99 systemically, or to the round window.96 Animal studies have not shown significant antitumor interference.106 One small-scale clinical trial showed complete otoprotection.107 Larger-scale clinical trials will be needed. |
| Ebselen | PO | Glutathione peroxidase promoter | In animal studies, ebselen, a selenium-containing compound, has reduced cisplatin-induced outer hair cell loss with and without allopurinol co-administration89 and does not appear to comprise cisplatin's antitumor efficacy.108 To date, ebselen has not been tested in clinical trials, but trials are in the planning stages. |
| Ringer's solution or dexamethasone | Intratympanic injection | Agent dependent (anti-inflammatory) | Compartmental therapy via tympanostomy tubes.92,95 |
Abbreviations: IV, intravenous; NAC, N-acetylcysteine; PO, orally; STS, sodium thiosulfate.