Method of reducing multi-drug resistance using inositol tripyrophosphate

Patent metadata

Field	Value
Publication number	US-2016235771-A1
Application number	US-201615145257-A
Country	US
Kind code	A1
Filing date	May 3, 2016
Priority date	Jul 7, 2009
Publication date	Aug 18, 2016
Grant date	—

Abstract

Inositol trisphosphate (ITPP) causes normalization of tumor vasculature and is a particularly effective cancer therapy when a second chemotherapeutic agent is administered following partial vascularization. ITPP also treats, alone or in combination, multi-drug resistant cancers. ITPP can also be used to reduce the amount of a second chemotherapeutic drug required for anticancer activity. In addition, ITPP enhances immune response and treats hyperproliferative disorders.

First claim

We claim:

1 . A method for treating cancer, comprising
administering to a subject in need thereof a therapeutically effective amount of ITPP; and administering to the subject a therapeutically effective amount of a chemotherapeutic agent following the partial vascular normalization in the tumor.

2 . The method of claim 1 , further comprising detecting the occurrence of partial vascular normalization in the tumor.

3 . The method of claim 3 , wherein the occurrence of partial vascular normalization is detected by measuring partial oxygen pressure (pO2) level of the tumor.

4 . The method of claim 1 , wherein the chemotherapeutic agent is administered in a sub-therapeutic dose.

5 . The method of claim 4 , wherein the sub-therapeutic dose of the chemotherapeutic agent is less than 70% of the approved label dose.

6 . A pharmaceutical composition comprising inositol trispyrophosphate (ITPP) and a chemotherapeutic agent selected from paclitaxel and cisplatin.

7 . The pharmaceutical composition of claim 6 , wherein the chemotherapeutic agent is paclitaxel.

8 . The pharmaceutical composition of claim 6 , wherein the chemotherapeutic agent is cisplatin.

9 . A treatment regimen for treating cancer in a subject, comprising administering simultaneously or sequentially a therapeutically effective amount of ITPP and a chemotherapeutic agent selected from paclitaxel and cisplatin.

10 . The treatment regimen of claim 9 , wherein the ITPP and the chemotherapeutic agent are administered simultaneously.

11 . The treatment regimen of claim 9 , wherein the ITPP and the chemotherapeutic agent are administered sequentially.

12 . The treatment regimen of claim 11 , wherein the ITPP is administered prior to the administration of the chemotherapeutic agent.

13 . The treatment regimen of any one of claims 9 - 12 , wherein the chemotherapeutic agent is paclitaxel.

14 . The treatment regimen of any one of claims 9 - 12 , wherein the chemotherapeutic agent is cisplatin.

15 . A pharmaceutical composition comprising inositol trispyrophosphate (ITPP) and a sub-therapeutic amount of a chemotherapeutic agent.

16 . The pharmaceutical composition of claim 15 , wherein the chemotherapeutic agent is selected from: aminoglutethimide, amsacrine, anastrozole, asparaginase, bcg, bicalutamide, bleomycin, buserelin, busulfan, camptothecin, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, clodronate, colchicine, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daunorubicin, dienestrol, diethylstilbestrol, docetaxel, doxorubicin, epirubicin, estradiol, estramustine, etoposide, exemestane, filgrastim, fludarabine, fludrocortisone, fluorouracil, fluoxymesterone, flutamide, genistein, goserelin, hydroxyurea, idarubicin, ifosfamide, imatinib, interferon, irinotecan, ironotecan, letrozole, leucovorin, leuprolide, levamisole, lomustine, mechlorethamine, medroxyprogesterone, megestrol, melphalan, mercaptopurine, mesna, methotrexate, mitomycin, mitotane, mitoxantrone, nilutamide, nocodazole, octreotide, oxaliplatin, paclitaxel, pamidronate, pentostatin, plicamycin, porfimer, procarbazine, raltitrexed, rituximab, streptozocin, suramin, tamoxifen, temozolomide, teniposide, testosterone, thioguanine, thiotepa, titanocene dichloride, topotecan, trastuzumab, tretinoin, vinblastine, vincristine, vindesine, and vinorelbine.

17 . The pharmaceutical composition of claim 16 , wherein the chemotherapeutic agent is selected from paclitaxel and cisplatin.

18 . The pharmaceutical composition of claim 17 , wherein the chemotherapeutic agent is paclitaxel.

19 . The pharmaceutical composition of claim 17 , wherein the chemotherapeutic agent is cisplatin.

20 . The pharmaceutical composition of claim 15 , wherein the sub-therapeutic dose of the chemotherapeutic agent is less than 70% of the approved label dose.

21 . A treatment regimen for treating cancer in a subject, comprising administering simultaneously or sequentially a therapeutically effective amount of ITPP and a sub-therapeutic amount of a chemotherapeutic agent.

22 . The treatment regimen of claim 21 , wherein the chemotherapeutic agent is selected from: aminoglutethimide, amsacrine, anastrozole, asparaginase, beg, bicalutamide, bleomycin, buserelin, busulfan, camptothecin, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, clodronate, colchicine, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daunorubicin, dienestrol, diethylstilbestrol, docetaxel, doxorubicin, epirubicin, estradiol, estramustine, etoposide, exemestane, filgrastim, fludarabine, fludrocortisone, fluorouracil, fluoxymesterone, flutamide, genistein, goserelin, hydroxyurea, idarubicin, ifosfamide, imatinib, interferon, irinotecan, ironotecan, letrozole, leucovorin, leuprolide, levamisole, lomustine, mechlorethamine, medroxyprogesterone, megestrol, melphalan, mercaptopurine, mesna, methotrexate, mitomycin, mitotane, mitoxantrone, nilutamide, nocodazole, octreotide, oxaliplatin, paclitaxel, pamidronate, pentostatin, plicamycin, porfimer, procarbazine, raltitrexed, rituximab, streptozocin, suramin, tamoxifen, temozolomide, teniposide, testosterone, thioguanine, thiotepa, titanocene dichloride, topotecan, trastuzumab, tretinoin, vinblastine, vincristine, vindesine, and vinorelbine.

23 . The treatment regimen of claim 22 , wherein the chemotherapeutic agent is selected from paclitaxel and cisplatin.

24 . The treatment regimen of claim 23 , wherein the chemotherapeutic agent is paclitaxel.

25 . The treatment regimen of claim 23 , wherein the chemotherapeutic agent is cisplatin.

26 . The treatment regimen of claim 21 , wherein the sub-therapeutic dose of the chemotherapeutic agent is less than 70% of the approved label dose.

27 . A method for treating cancer in a subject, comprising administering simultaneously or sequentially a therapeutically effective amount of ITPP and a sub-therapeutic amount of a chemotherapeutic agent.

28 . A method for treating a multi-drug resistant cancer in a subject, comprising administering a therapeutically effective amount of ITPP.

29 . The method of claim 28 , wherein the cancer is resistant to one or more of paclitaxel and cisplatin.

30 . A method for treating a hyper-proliferative condition comprising administering to a subject in need thereof a therapeutically effective amount of ITPP, wherein the hyper-proliferative condition is not cancer or characterized by undesired angiogenesis.

31 . The method of claim 30 , wherein the hyper-proliferative condition is selected from diabetic nephropathy, glomerulosclerosis, IgA nephropathy, cirrhosis, biliary atresia, congestive heart failure, scleroderma, radiation-induced fibrosis, lung fibrosis, psoriasis, genital warts and hyperproliferative cell growth diseases.

32 . The method of claim 30 , wherein the tissue or organ displaying the hyper-proliferative condition is hypoxic.

33 . The method of claim 30 , further comprising administering an additional antihyperproliferative agent.

34 . A method for enhancing immune response in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of ITPP, wherein the subject does not suffer from ca

Assignees

• Normoxys Inc
• Univ Strasbourg

Inventors

• Nicolau Yves Claude
• Lehn Jean-Marie
• Kieda Claudine

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P17/12

  Keratolytics, e.g. wart or anti-corn preparations · CPC title