Method for reducing ototoxicity in pediatric patients receiving platinum-based chemotherapy

Abstract

Described herein is a method for eliminating or reducing ototoxicity in patients receiving a platinum based chemotherapeutic. In particular, are methods of reducing ototoxicity in a pediatric patient. The methods described herein include administering an effective amount of sodium thiosulfate to a patient in need thereof to reduce ototoxicity.

We claim: 
     
         1 . A method of reducing the risk of developing cisplatin-induced hearing loss in a human pediatric patient less than about 2 years of age administered cisplatin to treat a localized and non-metastatic cancer, wherein the pediatric patient is also at risk for developing cisplatin-induced nephrotoxicity, the method comprising administering an effective amount of sodium thiosulfate about six hours after completing the administration of cisplatin;
 wherein the cisplatin is administered intravenously to the pediatric patient over a period of 6 hours or less;   wherein the administration of sodium thiosulfate does not lead to a significant reduction in glomerular filtration rate compared to a human pediatric patient less than about 2 years of age administered cisplatin to treat a localized and non-metastatic cancer but not administered sodium thiosulfate about six hours after completing the administration of cisplatin.   
     
     
         2 . The method of  claim 1 , wherein the administration of sodium thiosulfate does not lead to a reduction in glomerular filtration rate of grade 3 or higher as determined by National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). 
     
     
         3 . The method of  claim 1 , wherein the cancer is hepatoblastoma. 
     
     
         4 . The method of  claim 1 , wherein the cancer is neuroblastoma. 
     
     
         5 . The method of  claim 1 , wherein the cancer is medulloblastoma. 
     
     
         6 . The method of  claim 1 , wherein the cancer is osteosarcoma. 
     
     
         7 . The method of  claim 1 , wherein the cancer is a germ cell tumor. 
     
     
         8 . The method of  claim 1 , wherein cisplatin is administered to the pediatric patient on multiple days during a chemotherapeutic treatment cycle, and wherein the patient's sodium serum concentration is less than 145 mEq/L prior to each administration of the cisplatin and sodium thiosulfate. 
     
     
         9 . The method of  claim 8 , wherein cisplatin is administered to the pediatric patient on successive days during the chemotherapeutic treatment cycle 10 hours or longer after the completion of sodium thiosulfate administration the previous treatment day. 
     
     
         10 . The method of  claim 1 , wherein the pediatric patient receives a cumulative dose of cisplatin across all chemotherapeutic treatment cycles of greater than 200 mg/m2. 
     
     
         11 . The method of  claim 10 , wherein the cumulative dose of cisplatin is between 290 and 420 mg/m2. 
     
     
         12 . The method of  claim 1 , wherein the administration of sodium thiosulfate does not result in a significant increase in serum creatinine compared to a human pediatric patient less than about 2 years of age administered cisplatin to treat a localized and non-metastatic cancer but not administered sodium thiosulfate about six hours after completing the administration of cisplatin. 
     
     
         13 . The method of  claim 1 , wherein hearing loss is determined by:
 (i) a reduction in hearing measured by a ≥20 decibel (dB) at a single frequency;   (ii) a reduction in hearing measured by a ≥10 dB loss at two consecutive frequencies; or,   (iii) a reduction in hearing in three consecutive test frequencies where responses were previously obtained;   wherein hearing loss is assessed about 4 weeks following the last cisplatin administration.