Neuroblastoma treatment with taurolidine hydrolysis products

Abstract

Neuroblastoma is a tumor primarily affecting children. The current standard of care is not curative except in the rare case of a surgically-resectable lesion, although very high survival rates have been documented for low-risk neuroblastoma and moderate-risk neuroblastoma. Taurolidine was developed as an anti-infective, but it has been found to have surprising oncolytic activity in cell cultures and now in a rodent cancer model. The efficacy in rodent model is superior to the efficacy in cell culture. This invention relates to the use of taurolidine hydrolysis products (tarultam and/or taurinamide and/or methylene glycol and/or selected combinations thereof) for the treatment of neuroblastoma in juvenile mammals.

1 . A method for treating neuroblastoma, the method comprising:
 administering a composition to a patient, wherein the composition consists of at least one from the group consisting of:
 taurinamide; 
 taurultam; 
 methylene glycol; 
 taurultam and taurinamide in a ratio of 1 taurultam:7 taurinamide; and 
 taurultam, taurinamide and methylene glycol in a ratio of 1 taurultam:7 taurinamide:1 methylene glycol. 
   
     
     
         2 . A method according to  claim 1  wherein the composition consists of taurinamide. 
     
     
         3 . A method according to  claim 2  wherein the dose range is from 5 mg/kg to 280 mg/kg from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         4 . A method according to  claim 3  wherein the dose range is optimally from between 5 mg/kg and 60 mg/kg from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         5 . A method according to  claim 2  wherein the composition is administered in conjunction with an oncolytic agent and/or radiotherapy. 
     
     
         6 . A method according to  claim 1  wherein the composition consists of taurultam. 
     
     
         7 . A method according to  claim 6  wherein the dose range is from 5 mg/kg to 280 mg/kg from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         8 . A method according to  claim 7  wherein the dose range is optimally from between 5 mg/kg and 60 mg/kg from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         9 . A method according to  claim 6  wherein the composition is administered in conjunction with an oncolytic agent and/or radiotherapy. 
     
     
         10 . A method according to  claim 1  wherein the composition consists of methylene glycol. 
     
     
         11 . A method according to  claim 10  wherein the dose range is from 2.5 mg/kg to 160 mg/kg from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         12 . A method according to  claim 11  wherein the dose range is optimally from between 2.5 mg/kg and 30 mg/kg from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         13 . A method according to  claim 10  wherein the composition is administered in conjunction with an oncolytic agent and/or radiotherapy. 
     
     
         14 . A method according to  claim 1  wherein the composition consists of taurultam and taurinamide in a ratio of 1 taurultam:7 taurinamide. 
     
     
         15 . (canceled) 
     
     
         16 . A method according to  claim 14  wherein the composition is administered in conjunction with an oncolytic agent and/or radiotherapy. 
     
     
         17 . A method according to  claim 1  wherein the composition consists of taurultam, taurinamide and methylene glycol in a ratio of 1 taurultam:7 taurinamide:1 methylene glycol. 
     
     
         18 . A method according to  claim 17  wherein the taurultam, taurinamide and methylene glycol (in a ratio of 1 taurultam:7 taurinamide:1 methylene glycol) is given with a dosage range of Taurultam from 5 mg/kg to 280 mg/kg, with optimal range between 5 mg/kg and 40 mg/kg, combined with a dosage range of Taurinamide from 5 mg/kg to 280 mg/kg, with optimal range from 35 mg/kg to 40 mg/kg, further combined with methylene glycol with a dosage range of from 2.5 mg/kg to 160 mg/kg, with optimal range from 5 mg/kg to 40 mg/kg, from once daily through weekly, for an effective period of time based on individual patient response. 
     
     
         19 . A method according to  claim 17  wherein the composition is administered in conjunction with an oncolytic agent and/or radiotherapy. 
     
     
         20 . A method according to  claim 1  wherein the composition is delivered to the patient using one from the group consisting of parenteral delivery, intramuscular delivery and intravenous delivery. 
     
     
         21 . A method according to  claim 1  wherein the composition is included in a nanoparticle, and further wherein the nanoparticle is configured to delay hydrolysis of the composition until the nanoparticle reaches the site of a tumor. 
     
     
         22 . A method according to  claim 21  wherein the nanoparticle comprises a core of the composition and an exterior coating, wherein the exterior coating is configured to prevent exposure of the composition prior to arrival of the nanoparticle at the site of the tumor. 
     
     
         23 . A method according to  claim 22  wherein the exterior coating comprises an absorbable polymer or lipid which breaks down as the nanoparticle travels from the site of insertion to the site of the tumor. 
     
     
         24 . A method according to  claim 1  wherein the composition is delivered using a polymer system which is configured to delay hydrolysis of the composition. 
     
     
         25 . (canceled) 
     
     
         26 . A method according to  claim 1  wherein the composition comprises at least two from the group consisting of taurinamide, taurultam and methylene glycol. 
     
     
         27 . A method according to  claim 1  wherein the composition comprises all three from the group consisting of taurinamide, taurultam and methylene glycol.