Method of treating bendamustine-responsive conditions in patients requiring reduced volumes for administration

Abstract

Methods of treating bendamustine responsive conditions in patients having fluid and/or sodium intake restrictions are disclosed. The methods include identifying patients having such restrictions and in need of bendamustine, and then administering thereto a bendamustine-containing composition in a volume of about 100 ml or less intravenously over a period of about 30 minutes or less. The smaller volumes and reduced sodium load as compared to currently known methods of treatment minimize cardiac and/or renal stress in patients having diseases such as congestive heart failure or renal disease.

We claim: 
     
         1 . A method of treating a bendamustine-responsive condition in a subject, comprising:
 a) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition containing:
 i) from about 0.05 to about 12.5 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof; 
 ii) a solubilizer comprising polyethylene glycol and propylene glycol, the polyethylene glycol being present in an amount of from about 0.3 to about to 45% by volume and the propylene glycol being present in an amount of from about 0.03 to about 5% by volume; and, optionally 
 iii) a parenterally acceptable diluent; 
   over a period of less than or equal to about 30 minutes.   
     
     
         2 . The method of  claim 1 , wherein the parenterally acceptable diluent comprises 0.9% NaCl (normal saline), 0.45% NaCl (half normal saline) or 5% dextrose in water (D5W). 
     
     
         3 . The method of  claim 1 , wherein the subject has congestive heart disease or renal insufficiency. 
     
     
         4 . The method of  claim 1 , wherein the concentration of the bendamustine or pharmaceutically acceptable salt is from about 0.1 to about 3.2 mg/ml or from about 0.5 to about 5.6 mg/ml. 
     
     
         5 . The method of  claim 1 , wherein the amount of solubilizer is from about 0.5 to about 26.5% vol or from about 2.0 to about 22.4% vol. 
     
     
         6 . The method of  claim 1 , wherein the weight ratio of polyethylene glycol to propylene glycol is about 90:10 or about 85:15. 
     
     
         7 . The method of  claim 1 , wherein the volume administered is about 50, 30 or 15 ml. 
     
     
         8 . The method of  claim 1 , wherein the composition further comprises monothioglycerol and NaOH. 
     
     
         9 . The method of  claim 1 , wherein the composition is administered over a time period of about 15 minutes or less. 
     
     
         10 . The method of  claim 1 , wherein the bendamustine-responsive condition is chronic lymphocytic leukemia or indolent B-cell non-Hodgkin's lymphoma. 
     
     
         11 . A method of treating a bendamustine-responsive condition in a subject, comprising:
 a) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition, containing:
 i) from about 0.05 to about 12.5 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof; 
 ii) a solubilizer comprising polyethylene glycol and propylene glycol, the polyethylene glycol being present in an amount of from about 0.3 to about to 45% by volume and the propylene glycol being present in an amount of from about 0.03 to about 5% by volume; and, optionally 
 iii) a parenterally acceptable diluent; 
   once daily over a period of less than or equal to about 30 minutes;   wherein the amount of sodium included as part of the once daily administration is less than or equal to about 8-16 molar equivalents of sodium per 100 ml administration.   
     
     
         12 . The method of  claim 11 , wherein the volume administered is about 50 ml or less. 
     
     
         13 . The method of  claim 12 , wherein the amount of sodium included as part of the once daily administration less than or equal to about 4-8 molar equivalents of sodium per 50 ml administration. 
     
     
         14 . The method of  claim 11 , wherein the parenterally acceptable diluent comprises 0.9% NaCl (normal saline), 0.45% NaCl(half normal saline) or 5% dextrose in water (D5W). 
     
     
         15 . The method of  claim 11 , wherein the composition is administered over a time period of about 15 minutes or less. 
     
     
         16 . The method of  claim 11 , wherein the composition is administered over a time period of about 10 minutes or less. 
     
     
         17 . The method of  claim 13 , wherein the volume administered is about 30 ml or less. 
     
     
         18 . The method of  claim 17 , wherein the composition is administered over a time period of about 10 minutes or less. 
     
     
         19 . The method of  claim 13 , wherein the composition further comprises monothioglycerol and NaOH. 
     
     
         20 . The method of  claim 1 , wherein the bendamustine is present as the hydrochloride salt.