Method for Reducing Ototoxicity in Pediatric Patients Receiving Plantinum-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.

1 . A method of reducing the risk of developing cisplatin-induced hearing loss in a human pediatric patient administered cisplatin to treat a medulloblastoma tumor or a primitive neuro-ectodermal tumor (PNET), the method comprising administering an effective amount of sodium thiosulfate about six hours after completing the administration of an effective amount of cisplatin;
 wherein the cisplatin is administered intravenously to the pediatric patient over a period of 6 hours or less;   wherein the medulloblastoma or PNET pediatric patient is at least about 50% less likely to experience cisplatin-induced hearing loss than a medulloblastoma or PNET pediatric patient administered cisplatin to treat a medulloblastoma or PNET tumor but not administered sodium thiosulfate about six hours after completing the administration of cisplatin; and,   wherein the administration of sodium thiosulfate does not result in a significant difference in relapse free survival or overall survival in the medulloblastoma or PNET pediatric patient compared to a medulloblastoma or PNET pediatric patient administered cisplatin but not administered sodium thiosulfate.   
     
     
         2 . The method of  claim 1 , wherein the cisplatin-induced hearing loss is determined by:
 (i) a reduction in hearing measured by a≥20 decibel (dB) hearing loss at a single frequency;   (ii) a reduction in hearing measured by a≥10 dB hearing loss at two consecutive frequencies; or,   (iii) a reduction in hearing in three consecutive test frequencies; and,   wherein hearing loss is assessed about 4 weeks following cessation of cisplatin treatment and compared to a baseline hearing assessment occurring prior to initiation of cisplatin treatment.   
     
     
         3 . The method of  claim 1 , wherein the pediatric patient is between about 1 to 18 years of age. 
     
     
         4 . The method of  claim 1 , wherein the pediatric patient is less than 5 years of age. 
     
     
         5 . 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/m 2 . 
     
     
         6 . The method of  claim 5 , wherein the cumulative dose of cisplatin is between 290 and 420 mg/m 2 . 
     
     
         7 . The method of  claim 1 , wherein the pediatric patient has a weight of <5 kg, and the sodium thiosulfate is administered at a dose of about 10 g/m 2 . 
     
     
         8 . The method of  claim 1 , wherein the pediatric patient has a weight of between 5 and 10 kg, and the sodium thiosulfate is administered at a dose of about 15 g/m 2 . 
     
     
         9 . The method of  claim 1 , wherein the pediatric patient has a weight of >10 kg, and the sodium thiosulfate is administered at a dose of about 20 g/m 2 . 
     
     
         10 . The method of  claim 1 , wherein the pediatric patient has a medulloblastoma tumor. 
     
     
         11 . The method of  claim 1 , wherein the pediatric patient has a primitive neuro-ectodermal tumor (PNET). 
     
     
         12 . The method of  claim 1 , wherein the pediatric patient has received prior cranial irradiation.