Methods of otoprotection against platinum-based antineoplastic agents
AssigneeDecibel Therapeutics, Inc.
InventorsJohn Lee, John R. Soglia, Qi-Ying Hu, Fuxin Shi
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Abstract
Disclosed herein are methods for otoprotection against platinum-based antineoplastic agents by administering a thiosulfate salt to a subject in need thereof. Typically, the thiosulfate salt is administered to the subject scheduled to be administered a platinum-based antineoplastic agent within 4 hours. Alternatively, the thiosulfate salt is administered within 7 hours after the administration of a platinum-based neoplastic agent.
Claims17
A method of mitigating platinum-induced hearing loss in a human subject in need thereof, the method comprising (i) administering to the subject by intratympanically or transtympanically injecting an effective amount of a hypertonic composition having a calculated osmolarity of 3,000-7,000 mOsm/L and comprising 0.5M-1.0M of a thiosulfate salt, wherein the calculated osmolarity is calculated based on the thiosulfate salt and an optional tonicity agent, if present, and (ii) intravenously administering platinum-based antineoplastic agent to the subject 1 to 3 hours following step (i).
A hypertonic pharmaceutical composition having a calculated osmolarity of 400-1,500 mOsm/L and comprising 0.1 to 0.5M of an anti-platinum chemoprotectant agent, a liquid solvent, 5% to 20% (w/v) of a gelling agent relative to the liquid solvent, and an optional tonicity agent, wherein the calculated osmolarity is calculated based on the chemoprotectant agent and the tonicity agent, if present.
A method for determining a treatment window for intratympanic or transtympanic administration of a hypertonic composition comprising 0.5M-1.0M of a thiosulfate salt, the method comprising:
- a) providing a subject administered a hypertonic pharmaceutical composition comprising a thiosulfate salt by transtympanic or intratympanic injection;
- b) obtaining a perilymph sample from the subject;
- c) quantifying the concentration of thiosulfate salt in the perilymph sample using liquid chromatography with tandem mass spectrometry (LC-MS/MS);
- d) intravenously administering a platinum-based antineoplastic agent to the subject;
- e) repeating steps b) and c) one or more times;
- and
- f) calculating the half-life of thiosulfate in the perilymph.
Dependencies are inferred from the claim text.