Tyrosine kinase receptor antagonists and methods of treatment for breast cancer

• US 8,143,226 B2
• Filed: 10/25/2006
• Issued: 03/27/2012
• Est. Priority Date: 10/28/2005
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Campbell, Michael, Youngren, Jack F., Kushner, Peter, Goldfine, Ira, Kerner, John, Maddux, Betty A.
• Primary Examiner(s): Jiang, Shaojia Anna
• Assistant Examiner(s): Krishnan, Ganapathy
• Application Number:
  US11/552,686
• Publication Number:
  US 20070099847A1
• Time in Patent Office: 1,980 Days
• Field of Search: 514/23, 514/414, 514/23.414
• US Class Current: 514/23
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A method of treatment is disclosed whereby cancer cells are brought into contact with a formulation comprising an inhibitor of tyrosine kinase receptors. The formulation may be comprised of an injectable carrier and two or more tyrosine kinase receptor inhibitors which may be nordihydroguaiarectic acid (NDGA) and doxorubicin.

Claims

1. A method of treating a human breast cancer patient, wherein breast cancer cells in the cancer patient express Her2/neu receptor, comprising the steps of:

administering to the patient a therapeutically effective amount of a formulation comprising;

(1) a pharmaceutically acceptable carrier;

(2) nordihydroguaiaretic acid (NDGA) or pharmaceutically acceptable salts thereof; and

(3) doxorubicin, wherein the NDGA and doxorubicin act synergistically to inhibit growth of the breast cancer cells, and wherein doxorubicin and NDGA are administered in amounts below a therapeutically effective amount of either doxorubicin or NDGA when doxorubicin or NDGA are administered alone.

6. The method of claim 1, wherein the amount of doxorubicin administered is less than 60 mg/m² once in 21 days, or less than 30 mg/m² daily for 3 days every four weeks.

7. The method of claim 1, wherein the amount of NDGA is less than 100 mg/kg orally three times a week, or 37.5 mg/kg intraperitoneally three times a week.

2. A method of treating a human breast cancer patient, wherein breast cancer cells in the cancer patient do not express Her2/neu receptor, comprising the steps of:

administering to the patient a therapeutically effective amount of a formulation comprising;

(1) a pharmaceutically acceptable carrier;

(2) nordihydroguaiaretic acid (NDGA) or pharmaceutically acceptable salts thereof; and

(3) doxorubicin, wherein the NDGA and doxorubicin act synergistically to inhibit growth of the breast cancer cells, and wherein doxorubicin and NDGA are administered in amounts below a therapeutically effective amount of either doxorubicin or NDGA when doxorubicin or NDGA are administered alone.

8. The method of claim 2, wherein the amount of doxorubicin administered is less than 60 mg/m² once in 21 days, or less than 30 mg/m² daily for 3 days every four weeks.

9. The method of claim 2, wherein the amount of NDGA is less than 100 mg/kg orally three times a week, or 37.5 mg/kg intraperitoneally three times a week.

3. A method of treating breast cancer in a human patient, comprising the steps of:

contacting breast cancer cells of the patient with a formulation comprising a pharmaceutically acceptable carrier, a therapeutically effective amount of nordihydroguaiaretic acid (NDGA) and doxorubicin, wherein the NDGA and doxorubicin act synergistically to inhibit growth of the breast cancer cells; and

allowing the formulation to contact the cells for a sufficient period of time so as to result in death of the breast cancer cells, and wherein doxorubicin and NDGA are administered in amounts below a therapeutically effective amount of either doxorubicin or NDGA when doxorubicin or NDGA are administered alone.

4. The method of claim 3, wherein the amount of doxorubicin administered is less than 60 mg/m² once in 21 days, or less than 30 mg/m² daily for 3 days every four weeks.

5. The method of claim 3, wherein the amount of NDGA is less than 100 mg/kg orally three times a week, or 37.5 mg/kg intraperitoneally three times a week.

10. A method of treating a human breast cancer patient, wherein breast cancer cells in the cancer patient express Her2/neu receptor, comprising the steps of:

administering to the patient a therapeutically effective amount of a formulation comprising;

(1) a pharmaceutically acceptable carrier;

(2) nordihydroguaiaretic acid (NDGA) or pharmaceutically acceptable salts thereof; and

(3) doxorubicin, wherein the NDGA and doxorubicin act synergistically to inhibit growth of the breast cancer cells, and wherein the amount of doxorubicin administered is less than 60 mg/m² once in 21 days, or less than 30 mg/m² daily for 3 days every four weeks and the amount of NDGA is less than 100 mg/kg orally three times a week, or 37.5 mg/kg intraperitoneally three times a week.

11. A method of treating a human breast cancer patient, wherein breast cancer cells in the cancer patient do not express Her2/neu receptor, comprising the steps of:

administering to the patient a therapeutically effective amount of a formulation comprising;

(1) a pharmaceutically acceptable carrier;

(2) nordihydroguaiaretic acid (NDGA) or pharmaceutically acceptable salts thereof; and

(3) doxorubicin, wherein the NDGA and doxorubicin act synergistically to inhibit growth of the breast cancer cells, and wherein the amount of doxorubicin administered is less than 60 mg/m² once in 21 days, or less than 30 mg/m² daily for 3 days every four weeks and the amount of NDGA is less than 100 mg/kg orally three times a week, or 37.5 mg/kg intraperitoneally three times a week.

12. A method of treating breast cancer in a human patient, comprising the steps of:

contacting breast cancer cells of the patient with a formulation comprising a pharmaceutically acceptable carrier, a therapeutically effective amount of nordihydroguaiaretic acid (NDGA) and doxorubicin, wherein the NDGA and doxorubicin act synergistically to inhibit growth of the breast cancer cells, and wherein the amount of doxorubicin administered is less than 60 mg/m² once in 21 days or less than 30 mg/m² daily for 3 days every four weeks, and the amount of NDGA is less than 100 mg/kg orally three times a week or 37.5 mg/kg intraperitoneally three times a week; and

allowing the formulation to contact the cells for a sufficient period of time so as to result in death of the breast cancer cells.