Methods of treatment of cancer by continuous infusion of coenzyme Q10

Patent metadata

Field	Value
Publication number	US-9901542-B2
Application number	US-201414477828-A
Country	US
Kind code	B2
Filing date	Sep 4, 2014
Priority date	Sep 4, 2013
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

The invention provides regimens and methods for the treatment of cancer comprising continuous infusion of coenzyme Q10. The coenzyme Q10 may be administered as a monotherapy, or in combination with an additional agent, such as an anticancer agent, a chemotherapeutic agent, or an anti-angiogenic agent. The coenzyme Q10 may be administered at two or more different rates.

First claim

The invention claimed is:

1. A method of treating cancer in a subject, comprising administering a composition comprising coenzyme Q 10 by continuous intravenous infusion for at least 48 hours, wherein the coenzyme Q 10 is administered at two or more different rates and at a dose of at least 20 mg/kg/day (24 hours), thereby treating cancer in said subject.

2. The method of claim 1 , wherein the coenzyme Q10 is administered sequentially at a first rate and a second rate, wherein the first rate is higher than the second rate.

3. The method of claim 2 , further comprising administration of coenzyme Q10 at a third rate after the second rate.

4. The method of claim 3 , wherein the third rate is lower than the first rate and higher than the second rate.

5. The method of claim 2 , wherein the coenzyme Q10 is administered at the first rate for about 0.5 hours to about 3 hours.

6. The method of claim 1 , wherein the coenzyme Q10 is administered by continuous intravenous infusion for at least 72 hours, at least 96 hours, or at least 144 hours.

7. The method of claim 1 , wherein the continuous intravenous infusion is administered once per week.

8. The method of claim 1 , wherein the continuous infusion is administered twice per week.

9. The method of claim 2 , wherein the first rate is no more than 3.1 mg/kg/hr, no more than 4.2 mg/kg/hour, no more than 5.5 mg/kg/hour, no more than 7.4 mg/kg/hour, no more than 8.3 mg/kg/hour, no more than 9.2 mg/kg/hour, no more than 11.0 mg/kg/hour, no more than 11.2 mg/kg/hour, no more than 14 mg/kg/hour, no more than 14.5 mg/kg/hour, no more than 18.0 mg/kg/hour, no more than 18.4 mg/kg/hour, no more than 19.6 mg/kg/hour, no more than 22.9 mg/kg/hour, no more than 26.0 mg/kg/hour, no more than 28.7 mg/kg/hour, or no more than 35.8 mg/kg/hour.

10. A method of treating cancer in a subject, comprising:
(a) administering a composition comprising coenzyme Q 10 by continuous intravenous infusion for at least 48 hours, wherein the coenzyme Q 10 is administered at two or more different rates and at a dose of at least 20 mg/kg/day (24 hours);
(b) monitoring the subject for decreased coagulation; and
(c) discontinuing treatment with coenzyme Q 10 in a subject identified as having decreased coagulation, thereby treating cancer in said subject.

11. A method of treating cancer in a subject, comprising:
(a) administering a composition comprising coenzyme Q 10 by continuous intravenous infusion for at least 48 hours wherein the coenzyme Q 10 is administered at two or more different rates and at a dose of at least 20 mg/kg/day (24 hours);
(b) monitoring the subject for decreased coagulation;
(c) administering an agent to increase coagulation in a subject identified as having decreased coagulation;
(d) confirming the subject has normal coagulation; and
(e) continuing treatment with coenzyme Q 10 , thereby treating cancer in said subject.

12. A method of treating cancer in a subject, comprising:
(a) administering a composition comprising coenzyme Q 10 by continuous intravenous infusion for at least 48 hours, wherein the coenzyme Q 10 is administered at two or more different rates and at a dose of at least 20 mg/kg/day (24 hours);
(b) monitoring the subject for decreased coagulation; and
(c) continuing treatment with coenzyme Q 10 in a subject identified as having normal coagulation, thereby treating cancer in said subject.

13. The method of claim 1 , further comprising
(a) monitoring the subject for decreased coagulation, wherein the decreased coagulation comprises one or more of an International Normalized Ratio (INR) of greater than 2 and a platelet threshold less than 50,000/uL; and
(b) discontinuing treatment with coenzyme Q10 in a subject identified as having decreased coagulation.

14. The method of claim 1 , further comprising (a) monitoring the subject for decreased coagulation, wherein the decreased coagulation comprises one or more of an International Normalized Ratio (INR) of greater than 2, and a platelet threshold less than 50,000/uL;
(b) administering an agent to increase coagulation selected from the group consisting of Vitamin K, cryoprecipitate, and plasma in a subject identified as having decreased coagulation;
(c) confirming the subject has normal coagulation, wherein the normal coagulation comprises one or more of an International Normalized Ratio (INR) of 2 or less, and a platelet threshold of at least 50,000/uL; and
(d) continuing treatment with coenzyme Q10.

15. The method of claim 1 , further comprising
(a) monitoring the subject for decreased coagulation, wherein the decreased coagulation comprises one or more of an International Normalized Ratio (INR) of greater than 2, and a platelet threshold less than 50,000/uL; and
(b) continuing treatment with coenzyme Q10 in a subject identified as having normal coagulation, wherein the normal coagulation comprises one or more of an International Normalized Ratio (INR) of 2 or less, and a platelet threshold of at least 50,000/uL.

16. A method of preventing or limiting severity of an adverse event associated with treatment of cancer with intravenously administered coenzyme Q 10 , comprising administering to a subject having cancer a composition comprising coenzyme Q 10 by continuous intravenous infusion for at least 48 hours and at a dose of at least 20 mg/kg/day (24 hours), wherein the severity of adverse event in the subject is reduced as compared to intravenous administration of the same dose of coenzyme Q 10 over a period of 6 hours or less, thereby treating cancer in said subject.

17. The method of claim 13 , wherein the coenzyme Q10 is administered by continuous intravenous infusion for at least 72 hours, at least 96 hours, or at least 144 hours.

18. The method of claim 13 , wherein the continuous intravenous infusion dose is administered once per week or twice per week.

19. The method of claim 16 , wherein the adverse event comprises a coagulopathy.

20. The method of claim 16 , wherein the adverse event comprises a bleeding event.

21. The method of claim 1 , wherein the composition comprising coenzyme Q10 is administered by continuous intravenous infusion for about 96 hours, and wherein the composition is administered sequentially at a first rate, a second rate, and a third rate wherein:
(a) the first rate is a highest rate administered during the first hour of the continuous intravenous infusion;
(b) the second rate is a lowest rate administered during hours 2 to 48 of the continuous intravenous infusion; and
(c) the third rate is an intermediate rate between the first rate and the second rate and is administered during hours 49 to 96 of the continuous intravenous infusion.

22. The method of claim 1 , wherein the composition comprising coenzyme Q10 is administered by continuous intravenous infusion for about 144 hours, and wherein the composition is administered sequentially at a first rate, a second rate, and a third rate wherein:
(a) the first rate is a highest rate administered during the first hour of the continuous intravenous infusion;
(b) the second rate is a lowest rate administered during hours 2 to 72 of the continuous intravenous infusion; and
(c) the third rate is an intermediate rate between the first rate and the second rate and is administered during hours 73 to 144 of the continuous intravenous infusion.

23. The method of claim 21 or 22 , wherein the first rate is selected from the group consisting of no more than 3.1 mg/kg

Assignees

• Berg Llc

Inventors

• Narain Niven Rajin
• Sarangarajan Rangaprasad
• Gray Thomas Mitchell
• Mccook John Patrick
• Jimenez Joaquin J

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title