Method of treating bendamustine-responsive conditions in patients requiring reduced volumes for administration
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 120 ml or less intravenously over a period of about 15 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.
1. A method of treating chronic lymphocytic leukemia or indolent B cell non-Hodgkin lymphoma in a subject comprising:
parenterally administering to the subject, over a period of less than or equal to about 15 minutes, a dose of from about 25 mg/m 2 to about 120 mg/m 2 of bendamustine or a pharmaceutically acceptable salt thereof, wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is provided in a liquid composition comprising:
a total volume of about 100 ml or less;
bendamustine or a pharmaceutically acceptable salt thereof, at a concentration of from about 0.5 to about 5.6 mg/ml;
a solubilizer comprising polyethylene glycol and propylene glycol, wherein the amount of solubilizer is from about 0.5 to about 26.5% by volume;
a parenterally acceptable diluent; and optionally,
an antioxidant.
2. The method of claim 1 , wherein the subject is human.
3. The method of claim 1 , wherein the amount of solubilizer is from about 2.0 to about 22.4% vol.
4. The method of claim 1 , where the polyethylene glycol is PEG 400.
5. The method of claim 1 , wherein the concentration of bendamustine, or pharmaceutically acceptable salt thereof, in said liquid composition is from about 0.1 to about 3.2 mg/mL.
6. The method of claim 1 , wherein the weight ratio of polyethylene glycol to propylene glycol is about 90:10.
7. The method of claim 6 , wherein the volume of the liquid composition is about 50 ml.
8. The method of claim 1 , wherein the antioxidant is monothioglycerol.
9. The method of claim 1 , wherein the volume of the liquid composition is about 50 ml.
10. The method of claim 1 , wherein the subject is being treated for chronic lymphocytic leukemia.
11. The method of claim 10 , wherein the liquid composition is administered intravenously in a volume of about 50 ml over a period of 10 minutes or less on days 1 and 2 of a 28 day cycle.
12. The method of claim 11 , wherein the liquid composition is administered over a period of about 10 minutes.
13. The method of claim 11 , wherein the liquid composition is administered for up to 6 cycles.
14. The method of claim 10 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is from about 25 mg/m 2 to about 100 mg/m 2 .
15. The method of claim 10 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is about 100 mg/m 2 .
16. The method of claim 1 , wherein the subject is being treated for indolent B cell non-Hodgkin lymphoma.
17. The method of claim 16 , wherein the liquid composition is administered intravenously in a volume of about 50 ml over a period of about 10 minutes or less on days 1 and 2 of a 21 day cycle.
18. The method of claim 17 , wherein the liquid composition is administered over a period of about 10 minutes.
19. The method of claim 17 , wherein the composition is administered for up to 8 cycles.
20. The method of claim 16 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is from about 60 mg/m 2 to about 120 mg/m 2 to the subject.
21. The method of claim 16 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is about 120 mg/m 2 .
22. The method according to claim 1 , wherein the bendamustine is present as the hydrochloride salt.
23. A method of treating chronic lymphocytic leukemia or indolent B cell non-Hodgkin lymphoma in a subject consisting essentially of:
parenterally administering to the subject, over a period of less than or equal to about 15 minutes, a dose of from about 25 mg/m 2 to about 120 mg/m 2 of bendamustine or a pharmaceutically acceptable salt thereof, wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is provided in a liquid composition comprising:
a volume of about 100 ml or less;
bendamustine or a pharmaceutically acceptable salt thereof, at a concentration of from about 0.5 to about 5.6 mg/ml;
a solubilizer comprising polyethylene glycol and propylene glycol, wherein the amount of solubilizer is from about 0.5 to about 26.5% by volume;
a parenterally acceptable diluent; and optionally,
an antioxidant.