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 a bendamustine-responsive condition in a subject requiring restricted fluid and/or sodium intake, comprising
a) identifying a subject in need of bendamustine therapy and having a physiological condition requiring restricted fluid and/or sodium intake;
b) 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% volume and the propylene glycol being present in an amount of from about 0.03 to about 5% volume; and, optionally
iii) a parenterally acceptable diluent
over a substantially continuous period of less than or equal to about 30 minutes.
2. The method of claim 1 , wherein the diluent comprises 0.9% NaCl or 0.45% NaCl.
3. The method of claim 1 , wherein the subject has congestive heart disease.
4. The method of claim 1 , wherein the subject has renal insufficiency.
5. The method of claim 4 , wherein the renal insufficiency is renal failure or renal suppression.
6. 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.
7. The method of claim 1 , wherein the concentration of the bendamustine or pharmaceutically acceptable salt is from about 0.5 to about 5.6 mg/ml.
8. The method of claim 1 , wherein the amount of solubilizer is from about 0.5 to about 26.5% vol.
9. The method of claim 1 , wherein the amount of solubilizer is from about 2.0 to about 22.4% vol.
10. The method of claim 1 , where the polyethylene glycol is PEG 400.
11. The method of claim 1 , wherein the weight ratio of polyethylene glycol to propylene glycol is about 90:10.
12. The method of claim 1 , wherein the weight ratio of polyethylene glycol to propylene glycol is about 85:15.
13. The method of claim 1 , wherein the volume administered is about 50, 30 or 15 ml.
14. The method of claim 1 , wherein the composition further comprises monothioglycerol and NaOH.
15. The method of claim 7 , wherein the volume administered is about 50 ml+/−15% or less and the composition is administered over a time period of about 10 minutes or less.
16. The method of claim 6 , wherein the volume administered is about 100 ml+/−15% or less and the composition is administered over a time period of about 15 minutes or less.
17. The method of claim 1 , wherein the parenterally acceptable diluent is 0.9% NaCl (normal saline).
18. The method of claim 1 , wherein the bendamustine-responsive condition is chronic lymphocytic leukemia.
19. The method of claim 18 , wherein the composition is administered intravenously in a volume of about 50 ml over a time period of about 10 minutes or less on days 1 and 2 of a 28 day cycle.
20. The method of claim 18 , wherein the composition is administered intravenously in a volume of about 100 ml over a time period of about 15 minutes or less on days 1 and 2 of a 28 day cycle.
21. The method of claim 18 , wherein the composition is administered for up to 6 cycles.
22. The method of claim 18 , wherein the volume of the composition administered to the subject provides a dosage amount ranging from about 25 mg/m 2 to about 100 mg/m 2 to the subject.
23. The method of claim 1 , wherein the bendamustine-responsive condition is indolent B-cell non-Hodgkin's lymphoma.
24. The method of claim 23 , wherein the composition is administered intravenously in a volume of about 50 ml over a time period of about 10 minutes or less on days 1 and 2 of a 21 day cycle.
25. The method of claim 23 , wherein the composition is administered intravenously in a volume of about 100 ml over a time period of about 15 minutes or less on days 1 and 2 of a 21 day cycle.
26. The method of claim 23 , wherein the composition is administered for up to 8 cycles.
27. The method of claim 23 , wherein the volume of the composition administered to the subject provides a dosage amount ranging from about 60 mg/m 2 to about 120 mg/m 2 to the subject.
28. A method of treating a bendamustine-responsive condition in a subject requiring restricted fluid and/or sodium intake, comprising
a) identifying a subject in need of bendamustine therapy and having a physiological condition requiring restricted fluid and/or sodium intake;
b) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition containing:
Ingredient
Concentration Range (mg/ml)
Bendamustine HCl
0.05 to 1.6
Solubilizer 1 propylene glycol
0.3 to 6.5
Solubilizer 2 PEG 400
3.3 to 65
Monothioglycerol
0.02 to 0.35
NaOH
0.0 to 0.01
and, optionally a parenterally acceptable diluent, over a substantially continuous period of less than or equal to about 30 minutes.
29. A method of treating a bendamustine-responsive condition in a subject requiring restricted fluid and/or sodium intake, comprising
a) identifying a subject in need of bendamustine therapy and having a physiological condition requiring restricted fluid and/or sodium intake;
b) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition containing:
Ingredient
Concentration Range (mg/ml)
Bendamustine HCl
1.1 to 12.5
Solubilizer 1 propylene glycol
4.5 to 51
Solubilizer 2 PEG 400
45 to 500
Monothioglycerol
0.2 to 2.5
NaOH
0.0 to 0.04
and, optionally a parenterally acceptable diluent, over a substantially continuous period of less than or equal to about 30 minutes.
30. A method according to claim 1 , wherein the bendamustine is present as the hydrochloride salt.