Method of treating cancer using kinase inhibitors

• US 20040001833A1
• Filed: 06/04/2003
• Published: 01/01/2004
• Est. Priority Date: 06/05/2002
• Status: Active Grant

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Agus, David B.
• Granted Patent: US 7,384,940 B2
• Time in Patent Office: Days
• US Class Current: 424/146.1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Q 1/485 involving kinase
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57423 of lung
• CPC Class Codes: G01N 33/57434 of prostate

Abstract

Described herein are methods for treating cancer and other disease conditions in individuals who have either developed a resistance to conventional tyrosine kinase inhibitor (TKI) therapy or who are non-responsive ab initio to conventional TKI therapy. In various embodiments, the methods include administering to a patient a resistance-surmounting quantity of a TKI on a weekly or semi-weekly basis. Alternate embodiments of the present invention include a diagnostic method for assessing an individual'"'"'s probability of being resistant to TKI therapy, based upon an expression level of epithelial membrane protein-1 (EMP-1); one of the genes believed to be responsible for TKI resistance. The methods of the present invention may be particularly useful in the treatment of lung, breast, prostate, ovarian, brain and colon cancers. The methods of the present invention may be effective in blocking the HER-2 kinase domain either in addition to or in lieu of blocking the EGFR kinase domain.

Claims

1. A method for treating a disease condition in a patient resistant or non-responsive to conventional kinase inhibitor therapy, comprising:

providing a resistance-surmounting quantity of a kinase inhibitor; and

administering the resistance-surmounting quantity of the kinase inhibitor to the patient.

2. The method of claim 1, wherein the disease condition is cancer.

3. The method of claim 1, wherein the resistance-surmounting quantity of the kinase inhibitor is from about 500 mg to about 3,000 mg of the kinase inhibitor.

4. The method of claim 1, wherein the resistance-surmounting quantity of the kinase inhibitor is from about 1,500 mg to about 3,000 mg of the kinase inhibitor.

5. The method of claim 1, wherein the resistance-surmounting quantity of the kinase inhibitor is about 2,000 mg of the kinase inhibitor.

6. The method of claim 1, wherein administering a resistance-surmounting quantity of the kinase inhibitor further comprises administering the resistance-surmounting quantity of the kinase inhibitor at a time interval selected from the group consisting of once per week and twice per week.

7. The method of claim 1, wherein the kinase inhibitor is selected from the group consisting of Gefitinib (IRESSA), Erlotinib (TARCEVA), compound Cl1033, compound PKI166, compound GW2016, compound EKB569, compound IMC-C225, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable equivalent thereof, and a combination thereof.

8. The method of claim 1, wherein the resistance-surmounting quantity of the kinase inhibitor is an amount sufficient to block HER-2 kinase in the patient.

9. The method of claim 1, wherein the resistance-surmounting quantity of the kinase inhibitor is an amount sufficient to yield a serum concentration of at least about 800 μ

M in the patient.

10. The method of claim 1, wherein the resistance-surmounting quantity of the kinase inhibitor is an amount sufficient to block a kinase receptor in the patient other than EGFR or HER-2.

11. The method of claim 1, wherein administering the kinase inhibitor further includes administering the kinase inhibitor by an administration technique selected from the group consisting of orally, intravenous injection, and intramuscular injection.

12. The method of claim 2, wherein the cancer is a type of cancer selected from the group consisting of prostate cancer, lung cancer, breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, ovarian cancer, and a glioblastoma tumor.

13. A method of screening an individual for sensitivity to kinase inhibitor therapy, comprising:

examining an expression level of an EMP-1 gene in the individual; and

making a determination regarding sensitivity of the individual to conventional kinase inhibitor therapy based upon the expression level of the EMP-1 gene.

14. The method of claim 13, wherein making a determination regarding sensitivity further includes determining that the individual has a less than 10% probability of responding to conventional kinase inhibitor therapy when the expression level of the EMP-1 gene is detectable.

15. A method for treating a disease condition in an individual, comprising:

examining an expression level of an EMP-1 gene in the individual;

making a determination regarding sensitivity of the individual to conventional kinase inhibitor therapy based upon the expression level of the EMP-1 gene; and

administering a resistance-surmounting quantity of a kinase inhibitor to the individual.

16. The method of claim 15, wherein the disease condition is cancer.

17. The method of claim 15, wherein making a determination regarding sensitivity further includes determining that the individual has a less than 10% probability of responding to conventional kinase inhibitor therapy when the expression level of the EMP-1 gene is detectable.

18. The method of claim 15, wherein the resistance-surmounting quantity of the kinase inhibitor is from about 500 mg to about 3,000 mg of the kinase inhibitor.

19. The method of claim 15, wherein the resistance-surmounting quantity of the kinase inhibitor is from about 1,500 mg to about 3,000 mg of the kinase inhibitor.

20. The method of claim 15, wherein the resistance-surmounting quantity of the kinase inhibitor is about 2,000 mg of the kinase inhibitor.

21. The method of claim 15, wherein administering a resistance-surmounting quantity of the kinase inhibitor further comprises administering the resistance-surmounting quantity of the kinase inhibitor at a time interval selected from the group consisting of once per week and twice per week.

22. The method of claim 15, wherein the kinase inhibitor is selected from the group consisting of Gefitinib (IRESSA), Erlotinib (TARCEVA), compound CI1033, compound PKI166, compound GW2016, compound EKB569, compound IMC-C225, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable equivalent thereof, and a combination thereof.

23. The method of claim 15, wherein the resistance-surmounting quantity of the kinase inhibitor is an amount sufficient to block HER-2 kinase in the patient.

24. The method of claim 15, wherein the resistance-surmounting quantity of the kinase inhibitor is an amount sufficient to yield a serum concentration of at least about 800 μ

M in the patient.

25. The method of claim 15, wherein the resistance-surmounting quantity of the kinase inhibitor is an amount sufficient to block a kinase receptor in the patient other than EGFR or HER-2.

26. The method of claim 15, wherein administering the kinase inhibitor further includes administering the kinase inhibitor by an administration technique selected from the group consisting of orally, intravenous injection, and intramuscular injection.

27. The method of claim 16, wherein the cancer is a type of cancer selected from the group consisting of prostate cancer, lung cancer, breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, ovarian cancer, and a glioblastoma tumor.