Methods and compositions for the treatment of cancer

• US 20040072824A1
• Filed: 03/12/2003
• Published: 04/15/2004
• Est. Priority Date: 06/01/2001
• Status: Abandoned Application

• Current Assignee: Adam Telerman, Marius Tuijnder, Robert Amson
• Original Assignee: Adam Telerman, Marius Tuijnder, Robert Amson
• Inventors: Tuijnder, Marius, Telerman, Adam, Amson, Robert
• Application Number:
  US10/385,509
• Publication Number:
  US 20040072824A1
• Time in Patent Office: Days
• US Class Current: 514/225.8
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4515 having a butyrophenone group in position 1, e.g. haloperidol pipamperone A61K31/4545
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4965 Non-condensed pyrazines
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam

Abstract

Methods of treating and managing cancer are disclosed, which comprise the administration of an antihistaminic agents or structurally/functionally related to compound, optionally in combination with one or more additional anti-cancer agents. Pharmaceutical compositions, including single unit dosage forms, and kits useful in the treatment and management of cancer are disclosed. Also disclosed is a method of determining effectiveness of a cancer treatment.

Claims

1. A method of inhibiting the growth of a cancer cell, which comprises contacting the cell with an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

2. The method of claim 1, wherein the antihistaminic agent or structurally/functionally related compound is perphenazine, sertralin, thioridazine, chlorpromazine, paroxetine, flupentixol, fluphenazine, hydroxyzine or promethazine.

3. A method of treating cancer, which comprises administering to a patient in need of such treatment a therapeutically effective amount of an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

5. The method of claim 3 or 4 wherein the antihistaminic agent or structurally/functionally related compound is perphenazine, sertralin, thioridazine, chlorpromazine, paroxetine, flupentixol, fluphenazine, hydroxyzine or promethazine.

6. The method of claim 3 or 4 wherein the cancer is leukemia, lymphoma, melanoma, or cancer of the liver, lung, pancreas, stomach, thyroid, larygopharnx, skin, uterus, breast, colon, cervix, ovary, testis, prostate or rectum.

7. The method of claim 6 wherein the cancer is leukemia, melanoma, or cancer of breast, colon or lung.

8. The method of claim 3 or 4 wherein the cancer is primary or metastatic.

4. A method of managing cancer, which comprises administering to a patient in need of such management a prophylactically effective amount of an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

9. A method of treating cancer, which comprises administering to a patient in need of such treatment an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof, and a second anti-cancer agent, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

10. A method of managing cancer, which comprises administering to a patient in need of such management a prophylactically effective amount of an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof, and a second anti-cancer agent, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

11. The method of claim 9 or 10 wherein the antihistaminic agent or structurally/functionally related compound is perphenazine, sertralin, thioridazine, chlorpromazine, paroxetine, flupentixol, fluphenazine, hydroxyzine or promethazine.

12. The method of claim 9 or 10 wherein the cancer is leukemia, lymphoma, melanoma, or cancer of the liver, lung, pancreas, stomach, thyroid, larygopharnx, skin, uterus, breast, colon, cervix, ovary, testis, prostate or rectum.

13. The method of claim 12 wherein the cancer is leukemia.

14. The method of claim 13 wherein the second anti-cancer agent is prednisone, vincristine, anthracycline, asparaginase, cytarabine, etoposide, cyclophosphamide, methotrexate, leucovorin, cytosine arabinose, corticosteroids, daunorubicin, idarubicin, 6-thioguanine, chlorambucil, fludarabine, interferon α

, deoxyconformycin, 2-chlorodeoxyadenosine, hydroxyurea, 6-myelopurine, 6-thioguanine or melpharan.

15. The method of claim 12 wherein the cancer is melanoma.

16. The method of claim 15 wherein the second anti-cancer agent is dacarbazine, nitrosoureas carmustine, lomustine, cisplatin or interleukin-2.

17. The method of claim 12 wherein the cancer is breast cancer.

18. The method of claim 17 wherein the second anti-cancer agent is cyclophosphamide, 5-fluorouracil, methotrexate, doxorubicin, tamoxifen, progestins, aromatase inhibitors, aminoglutethimide, letrozole, paclitaxel, docetaxel, navelbine, capecitabine, mitomycin C, prednisone, taxane or vinblastine.

19. The method of claim 12 wherein the cancer is colon cancer.

20. The method of claim 19 wherein the second anti-cancer agent is fluorouracil, folinic acid, levamisole, leucovorin, oxaliplatin or irinotecan.

21. The method of claim 12 wherein the cancer is lung cancer.

22. The method of claim 21 wherein the second anti-cancer agent is cisplastin, topoisomerase inhibitors, carboplatin, vinorelbine, vincristine, vinblastine, docetaxel, oxaliplatin or paclitaxel.

23. A pharmaceutical composition comprising an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof, and a second anti-cancer agent, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

24. The pharmaceutical composition of claim 23, wherein the antihistaminic agent or structurally/functionally related compound is perphenazine, sertralin, thioridazine, chlorpromazine, paroxetine, flupentixol, fluphenazine, hydroxyzine or promethazine.

25. The pharmaceutical composition of claim 23, wherein the second anti-cancer agent is prednisone, vincristine, anthracycline, asparaginase, cytarabine, etoposide, cyclophosphamide, methotrexate, leucovorin, cytosine arabinose, corticosteroids, daunorubicin, idarubicin, 6-thioguanine, chlorambucil, fludarabine, interferon α

, deoxyconformycin, 2-chlorodeoxyadenosine, hydroxyurea, 6-myelopurine, melphalan, dacarbazine, nitrosoureas carmustine, lomustine, cisplatin, interleukin-2, 5-fluorouracil, doxorubicin, tamoxifen, progestins, aromatase inhibitors, aminoglutethimide, letrozole, paclitaxel, docetaxel, navelbine, capecitabine, mitomycin C, taxane, vinblastine, folinic acid, levamisole, irinotecan, topoisomerase inhibitors, carboplatin or vinorelbine.

26. A single unit pharmaceutical dosage form comprising an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof, and a second anti-cancer agent, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

27. A method of determining whether a cancer patient will respond to a cancer treatment comprising testing for overexpression of TPT1 gene in cancer cells from the patient, wherein the cancer treatment is administration of an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

28. The method of claim 27, wherein the antihistaminic agent or structurally/functionally related compound is perphenazine, sertralin, thioridazine, chlorpromazine, paroxetine, flupentixol, fluphenazine, Atranine A or Atranine C.

29. The method of claim 27, wherein the overexpression results in about 20% or more TCTP formation as compared with normal cells.

30. The method of claim 29, wherein the overexpression results in about 100% or more TCTP formation as compared with normal cells.

31. The method of claim 30, wherein the overexpression results in about 200% or more TCTP formation as compared with normal cells.

32. A method of determining effectiveness of a cancer treatment comprising:

obtaining cancer cells from a patient being treated at a first time and at a second time; and

determining if expression of TPT1 gene in cells obtained at the second time is less than the expression of TPT1 gene in cells obtained at the first time;

wherein the first time is earlier than the second time.

33. The method of claim 32, wherein the cancer treatment is administration of an antihistaminic agent or a structurally/functionally related compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate or clathrate thereof.

34. The method of claim 33, wherein the antihistaminic agent or structurally/functionally related compound is perphenazine, sertralin, thioridazine, chlorpromazine, paroxetine, flupentixol, fluphenazine, Atranine A or Atranine C.