Compositions and methods for cancer therapy

Patent metadata

Field	Value
Publication number	US-10052304-B2
Application number	US-201615291833-A
Country	US
Kind code	B2
Filing date	Oct 12, 2016
Priority date	Oct 12, 2015
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

The invention provides compositions and methods to treat a hyperproliferative disorder with ascorbate or a pharmaceutically acceptable salt thereof, at least one chelating agent that enhances ascorbate redox cycling (EDTA) to form H 2 O 2 , and one or more anti-cancer therapies.

First claim

The invention claimed is:

1. A method for treating a hyperproliferative disorder in a mammal, comprising administering to the mammal a combination of ascorbate, a chelating agent and an anti-cancer therapy, wherein the hyperproliferative disorder is non-small cell lung cancer, and pharmacological doses of ascorbate, calcium disodium EDTA, paclitaxel, and carboplatin are administered, wherein the ascorbate is administered at a dose of about 75 g-100 g infusion 2-5 times per week, calcium disodium EDTA is administered at a dose of about 35-50 mg/kg per day, paclitaxel is administered at a dose of about 200 mg/m 2 every 3 weeks, and carboplatin is administered at a dose of about AUC (area under the curve) 6 every 3 weeks.

2. The method of claim 1 , wherein the ascorbate and a chelating agent are administered for more than a month.

3. The method of claim 1 , wherein the ascorbate and calcium disodium EDTA is administered intravenously.

4. The method of claim 1 , wherein:
a) ascorbate or the pharmaceutically acceptable salt thereof and chelating agent are administered simultaneously with the one or more anti-cancer therapies; or
b) ascorbate or the pharmaceutically acceptable salt thereof and chelating agent and the one or more anti-cancer therapies are administered sequentially; or
c) administration of the one or more anti-cancer therapies begins about 1 to about 10 days before administration of the ascorbate or the pharmaceutically acceptable salt thereof and chelating agent; or
d) administration of ascorbate or the pharmaceutically acceptable salt thereof and chelating agent begins about 1 to about 10 days before administration of the one or more anti-cancer therapies; or
e) administration of ascorbate or the pharmaceutically acceptable salt thereof and chelating agent and administration of the one or more anti-cancer therapies begins on the same day.

5. The method of claim 1 , wherein the anti-cancer therapy is chemotherapy, immunotherapy, biologic therapy, or radiation therapy.

6. The method of claim 5 , wherein the radiation therapy is external beam or targeted radionuclide based therapy.

7. The combination of claim 6 , wherein the radiation therapy is administered at a dose of about 1.8 to 2 Gy for 25 or more fractions.

8. A method for treating a hyperproliferative disorder in a mammal, comprising administering to the mammal a combination of ascorbate, a chelating agent and an anti-cancer therapy, wherein the hyperproliferative disorder is sarcoma, and pharmacological doses of ascorbate, calcium disodium EDTA, and adriamycin or gemcitabine are administered.

9. The method of claim 8 , wherein the ascorbate is administered at a dosage of at least 75 g/day and the chelating agent is administered at a dosage of at least 35 mg/day.

10. The method of claim 8 , wherein the ascorbate is administered at a dose of about 75 g-100 g infusion 2-5 times per week, the calcium disodium EDTA is administered at a dose of about 35-50 mg/kg per day, and adriamycin is administered at a dose of about 75 mg/m 2 every 3 weeks or gemcitabine is administered at a dose of about 1000 mg/m 2 on day 1, day 8, and day 15, and then repeated after 3 weeks.

11. The method of claim 8 , wherein the ascorbate and a chelating agent are administered for more than a month.

12. The method of claim 8 , wherein the ascorbate and calcium disodium EDTA is administered intravenously.

13. The method of claim 8 , wherein:
a) ascorbate or the pharmaceutically acceptable salt thereof and chelating agent are administered simultaneously with the one or more anti-cancer therapies; or
b) ascorbate or the pharmaceutically acceptable salt thereof and chelating agent and the one or more anti-cancer therapies are administered sequentially; or
c) administration of the one or more anti-cancer therapies begins about 1 to about 10 days before administration of the ascorbate or the pharmaceutically acceptable salt thereof and chelating agent; or
d) administration of ascorbate or the pharmaceutically acceptable salt thereof and chelating agent begins about 1 to about 10 days before administration of the one or more anti-cancer therapies; or
e) administration of ascorbate or the pharmaceutically acceptable salt thereof and chelating agent and administration of the one or more anti-cancer therapies begins on the same day.

14. The method of claim 8 , wherein the anti-cancer therapy is chemotherapy, immunotherapy, biologic therapy, or radiation therapy.

15. The method of claim 14 , wherein the radiation therapy is external beam or targeted radionuclide based therapy.

16. The combination of claim 14 , wherein the radiation therapy is administered at a dose of about 1.8 to 2 Gy for 25 or more fractions.

Assignees

• Univ Iowa Res Found

Inventors

• Allen Bryan G
• Spitz Douglas R
• Buettner Garry R
• Cullen Joseph
• Schoenfeld Joshua
• Schultz Michael
• Zhan Fenghuang

Classifications

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K31/295

  Iron group metal compounds · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K45/06

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

• A61K31/198

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title