Combination therapy of coenzyme q10 and radiation for treatment of glioma

Patent metadata

Field	Value
Publication number	US-2021322339-A1
Application number	US-202017100674-A
Country	US
Kind code	A1
Filing date	Nov 20, 2020
Priority date	Nov 20, 2019
Publication date	Oct 21, 2021
Grant date	—

Abstract

The invention provides methods and compositions for treatment of a subject with a glioma. The methods comprise administering a composition comprising Coenzyme Q10 to the subject by continuous intravenous infusion; and administering radiation therapy to the subject. The composition comprising Coenzyme Q10 may be administered to the subject by continuous intravenous infusion for at least 24 hours before the radiation therapy is initiated.

First claim

1 . A method of treating a glioma in a subject comprising:
(a) administering a composition comprising Coenzyme Q10 to the subject by continuous intravenous infusion; and (b) administering radiation therapy to the subject, wherein the composition comprising Coenzyme Q10 is administered to the subject by continuous intravenous infusion for at least 24 hours before the radiation therapy is initiated, thereby treating the glioma in the subject.

2 . The method of claim 1 , wherein the composition comprising Coenzyme Q10 is administered to the subject by continuous intravenous infusion for at least 48 hours, at least 72 hours, or at least 96 hours before the radiation therapy is initiated.

3 . The method of claim 1 , wherein at least two doses of the composition comprising Coenzyme Q10 are administered to the subject by continuous intravenous infusion before the radiation therapy is initiated.

4 . The method of claim 3 , wherein each of the at least two doses is administered once per week.

5 . The method of claim 1 , wherein the radiation therapy is initiated at least one week after administration of the composition comprising Coenzyme Q10 is initiated.

6 . (canceled)

7 . The method of claim 1 , wherein the glioma is an anaplastic astrocytoma or a glioblastoma.

8 . The method of claim 7 , wherein the glioblastoma is a gliosarcoma.

9 . The method of claim 1 , wherein the subject has undergone surgery for the glioma before administration of the composition comprising Coenzyme Q10 is initiated.

10 . The method of claim 1 , wherein the subject has not been treated with an anticancer agent for the glioma before administration of the composition comprising Coenzyme Q10 is initiated.

11 . The method of claim 10 , wherein the anticancer agent is selected from temozolomide (TMZ) and bevacizumab.

12 . The method of claim 1 , wherein the subject has not been treated with radiation therapy for the glioma before administration of the composition comprising Coenzyme Q10 is initiated.

13 . The method of claim 1 , wherein the subject demonstrates a clinical benefit selected from the group consisting of stable disease per RECIST 1.1 criteria, partial response per RECIST 1.1 criteria, and complete response per RECIST 1.1 criteria as a result of administration of the composition comprising the Coenzyme Q10 compound and the radiation therapy.

14 - 17 . (canceled)

18 . The method of claim 1 , wherein the glioma comprises a Stage I tumor, a Stage II tumor, or a Stage III tumor.

19 - 20 . (canceled)

21 . The method of claim 1 , wherein the glioma comprises a Stage IV tumor.

22 . The method of claim 1 , wherein the glioma is a low grade glioma.

23 . The method of claim 1 , wherein the glioma is a high grade glioma.

24 - 25 . (canceled)

26 . The method of claim 1 , wherein the Coenzyme Q10 is administered at a dose of at least 50 mg/kg/week, at least 66 mg/kg/week, at last 88 mg/kg/week or at least 110 mg/kg/week.

27 . (canceled)

28 . The method of claim 1 , wherein the Coenzyme Q10 is administered at a dose selected from the group consisting of at least 50 mg/kg/dose, at least 66 mg/kg/dose, at least 88 mg/kg/dose, or at least 110 mg/kg/dose.

29 - 31 . (canceled)

32 . The method of claim 1 , wherein the radiation therapy is administered at a total dose of 0.1 to 100 Gy.

33 . The method of claim 1 , wherein the radiation therapy is administered at a rate of 10 to 5000 cGy/min.

34 . The method of claim 1 , wherein the subject is human.

35 . The method of claim 1 , further comprising administering an additional cancer therapy to the subject.

36 . The method of claim 35 , wherein the additional cancer therapy comprises exposing the glioma to an alternating electrical field.

37 . The method of claim 35 , wherein the additional cancer therapy comprises administration of one or more anticancer agents to the subject.

38 . The method of claim 37 , wherein the one or more anticancer agents is selected from the group consisting of temozolomide (TMZ) and bevacizumab.

39 - 40 . (canceled)

41 . The method of claim 1 , wherein the method further comprises administering Vitamin K1 to the subject.

42 . The method of claim 1 , wherein the subject exhibits an increase in one or more of overall survival and progression free survival relative to a subject that is administered the pharmaceutical composition comprising Coenzyme Q10 alone, or the radiation therapy alone.

43 . The method of claim 1 , wherein the composition comprising Coenzyme Q10 and the radiation therapy have a synergistic effect in treating the glioma.

Assignees

• Berg Llc

Inventors

• Narain Niven Rajin
• Sarangarajan Rangaprasad

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61N1/40

  Applying electric fields by inductive or capacitive coupling (microwave apparatus A61N5/00); {Applying radio-frequency signals} · CPC title

• A61K41/0038

  Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title