Treatment of gliomas using organonitro compound combination therapy
The invention provides therapeutic methods and kits for treating a glioma using a particular dosing regimen of the organonitro compound ABDNAZ, radiation therapy, and one of temozolomide, irinotecan, or bevacizumab.
1. A method of treating a glioma in a patient, comprising the steps of:
(a) administering to the patient in need thereof a therapeutically effective amount of a formulation comprising temozolomide, and within about 2 days thereafter subjecting the glioma to radiation therapy; and
(b) administering to the patient at least one dose of a therapeutically effective amount of a formulation comprising a compound ABDNAZ within about 7 days of administration of a first dose of the temozolomide; to treat the glioma;
wherein each dose of the formulation comprising the compound ABDNAZ is administered to the patient by intravenous infusion providing the compound ABDNAZ in an amount of from about 0.1 mg to about 20 mg; and
wherein the compound ABDNAZ has the chemical structure:
2. The method of claim 1 , wherein the formulation comprising temozolomide is administered daily for at least 2 weeks.
3. The method of claim 1 , wherein the patient receives temozolomide by oral administration at a daily dose of at least 50 mg/m 2 .
4. The method of claim 1 , wherein for a duration of at least 2 weeks following administration of the first dose of temozolomide, the patient receives at least one dose each week of a therapeutically effective amount of a formulation comprising the compound ABDNAZ.
5. The method of claim 1 , wherein two doses of a therapeutically effective amount of a formulation comprising the compound ABDNAZ are administered within about 7 days of administration of the first dose of temozolomide.
6. The method of claim 1 , wherein for a duration of at least 2 weeks following administration of the first dose of temozolomide, the patient receives two doses each week of a therapeutically effective amount of a formulation comprising the compound ABDNAZ.
7. The method of claim 1 , wherein the formulation comprising the compound ABDNAZ contains dimethylacetamide, water, and a polyethylene glycol.
8. The method of claim 7 , wherein the polyethylene glycol has a number-average molecular weight of about 400 g/mol.
9. The method of claim 1 , wherein the glioma is subjected to radiation therapy once per day for at least 3 days within a 7 day period following administration of the first dose of temozolomide.
10. The method of claim 1 , wherein the glioma is subjected to radiation therapy once per day for at least 5 days within a 7 day period following administration of the first dose of temozolomide.
11. The method of claim 1 , wherein when radiation therapy is administered to the glioma, the amount of radiation provided to the glioma on the day of administering the radiation therapy is from about 1 Gy to about 3 Gy.
12. The method of claim 1 , wherein after receiving temozolomide for a duration of 6 weeks, the patient does not receive any of temozolomide, radiation therapy, or the compound ABDNAZ for a duration of at least about 2 weeks.
13. The method of claim 1 , wherein after receiving temozolomide for a duration of 6 weeks, the patient does not receive any of temozolomide, radiation therapy, or the compound ABDNAZ for a duration of at least about 4 weeks.
14. A method of treating a glioma in a patient, comprising the steps of:
(a) administering to the patient in need thereof a therapeutically effective amount of a formulation comprising irinotecan, and within about 7 days subjecting the glioma to radiation therapy; and
(b) administering to the patient at least one dose of a therapeutically effective amount of a formulation comprising a compound ABDNAZ within about 7 days of administration of a first dose of the irinotecan; to treat the glioma;
wherein each dose of the formulation comprising the compound ABDNAZ is administered to the patient by intravenous infusion providing the compound ABDNAZ in an amount of from about 0.1 mg to about 20 mg; and
wherein the compound ABDNAZ has the chemical structure:
15. The method of claim 14 , wherein the glioma is an astrocytoma.
16. The method of claim 14 , wherein the glioma is a malignant astrocytoma.
17. The method of claim 14 , wherein the glioma is a glioblastoma.
18. The method of claim 14 , wherein the patient is an adult human.
19. The method of claim 14 , wherein there is at least a 35% reduction in the size of at least one glioma tumor in the patient.
20. The method of claim 14 , wherein there is at least a 35% reduction in the number of glioma tumors in the patient.