Use of ccr5 antagonists alone or in combination therapy for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-2018289689-A1
Application number	US-201515522113-A
Country	US
Kind code	A1
Filing date	Oct 27, 2015
Priority date	Oct 27, 2014
Publication date	Oct 11, 2018
Grant date	—

Abstract

The present invention relates to CCRS antagonists for use in the treatment of cancer, either in monotherapy or in combination therapy. The invention also relates to methods for determining whether a subject suffering from cancer benefits from an ongoing therapeutic treatment with a CCRS antagonist or whether a subject suffering from cancer will benefit from a planned therapeutic treatment with a CCRS antagonist.

First claim

1 . A method for treatment of cancer, wherein an amount effective to treat the cancer of a CCR5 antagonist is administered to a subject receiving at least one further anti-cancer therapy.

2 . The method according to claim 1 , wherein said cancer is selected from the group consisting of primary pancreatic cancer, metastatic pancreatic cancer, primary colorectal cancer, metastatic colorectal cancer, primary ovarial cancer, metastatic ovarial cancer, primary renal cell cancer, metastatic renal cell cancer, primary stomach cancer, metastatic stomach cancer, primary prostate cancer, metastatic prostate cancer, primary breast cancer, metastatic breast cancer, primary hepatocellular cancer, metastatic hepatocellular cancer, primary lung cancer, metastatic lung cancer, primary head and neck cancer, metastatic head and neck cancer, primary gastric cancer, metastatic gastric cancer, primary esophageal cancer, and metastatic esophageal cancer.

3 . The method according to claim 1 , wherein said at least one further anti-cancer-therapy is selected from the group consisting of
chemotherapy, radiation therapy, vaccination, immunotherapy, immunomodulatory therapy, stem cell therapy, anti-hormonal therapy, local ablation of metastases or tumors by physical intervention, and combinations of any of the above.

4 . The method according to claim 1 , wherein said at least one further anti-cancer-therapy comprises chemotherapy, and wherein the chemotherapy comprises the administration of an alkylating agent, an antimetabolite, folinic acid, a folate antagonist, a mitotic inhibitor, an anthracyclin, a topoisomerase inhibitor, an antibody, a signal transduction inhibitor, an inhibitor of angiogenesis, and an inhibitor of histone deacetylase.

5 . The method according to claim 4 , wherein said chemotherapy comprises the administration of an alkylating agent, wherein the alkylating agent is selected from the group consisting of bendamustin, busulfan, carboplatin, carmustin, cisplatin, oxaliplatin, cyclophosphamid, mitomycin, and treosulfan.

6 . The method according to claim 4 , wherein said chemotherapy comprises the administration of an antimetabolite, and wherein the antimetabolite is selected from the group consisting of 5-fluorouracil, capecitabin, cytarabin, gemcitabin, mercaptopurin, and deoxy glucose.

7 . The method according to claim 4 , wherein said chemotherapy comprises the administration of a folate antagonist, and wherein the folate antagonist is selected from the group consisting of methotrexate and pemetrexed.

8 . The method according to claim 4 , wherein said chemotherapy comprises the administration of a mitotic inhibitor, and wherein the mitotic inhibitor is selected from the group consisting of taxanes and vinca-alcaloids.

9 . The method according to claim 8 , wherein said mitotic inhibitor comprises a taxane, and wherein the taxane is selected from the group consisting of cabzitaxel, docetaxel, and paclitaxel.

10 . The method according to claim 4 , wherein said chemotherapy comprises the administration of an anthracyclin, and wherein the anthracyclin is selected from the group consisting of bleomycin, doxorubicin, mitoxantron, and epirubicin.

11 . The method according to claim 4 , wherein said chemotherapy comprises the administration of a topoisomerase inhibitor, and wherein the topoisomerase inhibitor is selected from the group consisting of campthotecin-derivatives and podophyllin-derivatives.

12 . The method according to claim 11 , wherein said topoisomerase inhibitor comprises a campthotecin-derivative, and wherein the campthotecin-derivative is selected from the group consisting of irinotecan and topotecan.

13 . The method according to claim 4 , wherein said chemotherapy comprises the administration of an antibody, and wherein the antibody is selected from the group consisting of bevacizumab (Avastin), cetuximab (Erbitux), panitumumab (Vectibix), ipilimumab, nivulomumab, tremelimumab, anti-OX40-antibodies, catumaxomab, and anti-CD40L antibodies.

14 . The method according to claim 4 , wherein said chemotherapy comprises the administration of a signal transduction inhibitor, and wherein the signal transduction inhibitor is selected from the group consisting of axatinib, crizotinib, erlotinib, sunitinib, sorafenib, everolimus, imatinib, lapatinib, pazopanib, temsirolimus, and vemurafenib.

15 . The method according to claim 4 , wherein said chemotherapy comprises the administration of an inhibitor of angiogenesis, and wherein the inhibitor of angiogenesis is aflibercept.

16 . The method according to claim 4 , wherein said chemotherapy comprises the administration of an inhibitor of histone deacetylase, and wherein the inhibitor of histone deacetylase is vorinostat.

17 . The method according to claim 1 , wherein said CCR5 antagonist is selected from the group consisting of Maraviroc, Vicriviroc, Aplaviroc, ancriviroc, [3H]maraviroc, [3H]ancriviroc, CCL7, TAK-779, E913, TAK-652, TAK-220, and vMIP-II.

18 . The method according to claim 1 , wherein said CCR5 antagonist is to be administered in an amount of between about 150 mg and about 600 mg once or twice a day.

19 . A method for treatment of metastases of colorectal carcinoma, wherein an amount effective to treat the metastases of colorectal carcinoma of a CCR5 antagonist is administered to a subject in need thereof.

20 . The method according to claim 19 , wherein the metastases are selected from the group consisting of liver metastases, lung metastases, bone metastases, pancreas metastases, lymph node metastases, and peritoneal metastases.

21 . The method according to claim 19 , wherein said CCR5 antagonist is selected from the group consisting of Maraviroc, Vicriviroc, Aplaviroc, ancriviroc, [3H]maraviroc, [3H]ancriviroc, CCL7, TAK-779, E913, TAK-652, TAK-220, and vMIP-II.

22 . The method according to claim 19 , wherein said CCR5 antagonist is to be administered in an amount of between about 150 mg and about 600 mg once or twice a day.

23 . A method for determining whether a subject benefits from a therapeutic treatment of cancer by a CCR5 antagonist, said method comprising the steps of:
comparing the level of at least one cytokine in a test sample isolated from a subject undergoing therapeutic treatment of cancer by a CCR5 antagonist to the level of the same cytokine in a test sample isolated from the same subject prior to said therapeutic treatment, wherein a reduction of the level of said at least one cytokine demonstrates that the subject benefits from said therapeutic treatment.

24 . The method according to claim 23 , wherein
(i) the cytokine is selected from the group consisting of MIF, IL-8, HGF, SCGF, IL-1ra, MCP-1, VEGF and VCAM-1, and/or (ii) the cancer is selected from the group consisting of primary pancreatic cancer, metastatic pancreatic cancer, primary colorectal cancer, metastatic colorectal cancer, primary ovarial cancer, metastatic ovarial cancer, primary renal cell cancer, metastatic renal cell cancer, primary stomach cancer, metastatic stomach cancer, primary prostate cancer, metastatic prostate cancer, primary breast cancer, metastatic breast cancer, primary hepatocellular cancer, metastatic hepatocellular cancer, primary lung cancer, metastatic lung cancer, primary head and neck cancer, metastatic head and neck cancer, primary gastric cancer, metastatic gastric cancer, primary esophageal cancer, and metastatic esophageal cancer, and/or (ii

Assignees

• Univ Heidelberg Ruprecht Karls

Inventors

• Halama Niels
• JÄGER Dirk
• Zoernig Inka
• Grabe Niels

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P13/12

  of the kidneys · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title