EP2063963A2 - Verfahren zur krebsbehandlung mit verabreichung einer vitamin-d-verbindung und eines zusätzlichen therapeutischen mittels - Google Patents
Verfahren zur krebsbehandlung mit verabreichung einer vitamin-d-verbindung und eines zusätzlichen therapeutischen mittelsInfo
- Publication number
- EP2063963A2 EP2063963A2 EP07837327A EP07837327A EP2063963A2 EP 2063963 A2 EP2063963 A2 EP 2063963A2 EP 07837327 A EP07837327 A EP 07837327A EP 07837327 A EP07837327 A EP 07837327A EP 2063963 A2 EP2063963 A2 EP 2063963A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- day
- therapeutically effective
- effective amount
- vitamin
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- compositions for treating cancer comprise administering a vitamin D compound in combination with at least one additional therapeutic agent, such as an anti-cancer agent or a steroid.
- additional therapeutic agent such as an anti-cancer agent or a steroid
- compositions comprising vitamin D compounds and at least one additional therapeutic agent, such as an anti-cancer agent or a steroid, e.g. , corticosteroid or, more specifically, a glucocorticoid.
- cancer is the second leading case of death in the United States after heart disease. Incidences of cancer are widely expected to increase as the U.S. population ages and, if current trends continue, cancer is expected to be the leading cause of the death by the year 2010. As of now, it is estimated that one in every two men in the United States will be diagnosed with cancer at some time during his lifetime and one in three women in the United States will be diagnosed with cancer at some time during her lifetime. Of special interest, are individuals diagnosed with prostate cancer and breast cancer since, along with lung cancer, prostate cancer and breast cancer are the most common and fatal forms of cancer.
- Prostate cancer is currently the most common non-skin cancer and the second leading cause of cancer-related death in men after lung cancer.
- the primary course of treatment for patients diagnosed with organ-confined prostate cancer is usually prostatectomy or radiotherapy. Not only are these treatments highly invasive and have undesirable side effects, such localized treatments are not effective on prostate cancer after it has metastasized. Moreover, a large percent of individuals who receive localized treatments will suffer from recurring cancer.
- breast cancer is the most common cancer among white and
- African-American women Similar to treating prostate cancer, most options for women diagnosed with breast cancer are highly invasive and have significant side-effects. Such treatments include surgery, radiation and chemotherapy. [0005J Another treatment option for individuals with cancer comprises administering vitamin D alone or in combination with chemotherapy or radiotherapy treatments. Vitamin D has been found to inhibit cell growth and stimulate cell differentiation in several in vitro and in vivo cancer models.
- vitamin D as a therapeutic agent
- hypercalcemia is a higher than normal level of calcium in the blood that can cause nausea, vomiting, confusion, lethargy, fatigue, excessive thirst, abdominal pain, constipation and muscle weakness.
- the use of vitamin D in clinical trials has been hampered by its ability to induce hypercalcemia at serum concentrations required to suppress cancer cell proliferation.
- Described herein are methods for treating a cancer in which a therapeutically effective amount of a vitamin D compound, such as seocalcitol, is administered to a patient, e.g., a patient in need thereof, in combination with a therapeutically effective amount of at least one additional therapeutic agent including, but not limited to, an anti-cancer agent or steroid.
- a therapeutically effective amount of a vitamin D compound such as seocalcitol
- the method is directed to treating a refractory cancer in a patient in which a therapeutically effective amount of a vitamin D compound, such as seocalcitol, is administered to a patient currently receiving another cancer treatment, e.g., the administration of an additional anti-cancer agent.
- a vitamin D compound such as seocalcitol
- the vitamin D compound is a non-hypercalcemic vitamin D compound analog, such as seocalcitol.
- the vitamin D compound can be administered by pulse administration.
- the method is directed to the treatment of a cancer in a mammal by administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.1 mg/m 2 to about 20 mg/m 2 of mitoxantrone.
- the method is directed to the treatment of a cancer in a mammal by administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 1 mg/m 2 to about 175 mg/m 2 of paclitaxel.
- the method is directed to the treatment of a cancer in a mammal by administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 1 mg/m 2 to about 100 mg/m 2 of docetaxel.
- the method for the treatment of a cancer in a mammal can also comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.01 mg to about 200 mg of leuprolide, wherein the leuprolide is administered over a period of about 3 days to about 12 months.
- the method can also comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.01 mg to about 20 mg of goserelin, wherein the goserelin is administered over a period of about 28 days to about 3 months.
- the treatment of a cancer in a mammal can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.01 mg to about 20 mg of triptorelin, wherein the triptorelin is administered over a period of about 1 month.
- the method for the treatment of a cancer in a mammal comprises administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.4 mg/day to about 10,000 mg/day of abiraterone acetate.
- the method for the treatment of a cancer in a mammal comprises administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 1 mg/day to about 300 mg/day of bicalutamide.
- the method for the treatment of a cancer in a mammal can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 1 mg/day to about 2000 mg/day of flutamide.
- the method for the treatment of a cancer in a mammal can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.01 mg/day to about 500 mg/day of a glucocorticoid including, but not limited to, hydrocortisone, prednisone or dexamethasone.
- compositions for the treatment of cancer that comprise a combination of a therapeutically effective amount of a vitamin D compound, such as seocalcitol, and a therapeutically effective amount of an additional anti-cancer agent, such as, but not limited to, mitoxantrone, paclitaxel, docetaxel, leuprolide, goserelin, triptorelin, abiraterone acetate, .bicalutamide, flutamide or a steroid, including, but not limited to, hydrocortisone, prednisone or dexamethasone.
- a vitamin D compound such as seocalcitol
- an additional anti-cancer agent such as, but not limited to, mitoxantrone, paclitaxel, docetaxel, leuprolide, goserelin, triptorelin, abiraterone acetate, .bicalutamide, flutamide or a steroid, including, but not limited to, hydrocortisone,
- kits comprising at least one vitamin D compound and an additional anti-cancer agent or steroid are contemplated.
- the kit may include a vial containing seocalcitol and another vial containing a glucocorticoid.
- cancer refers to the growth, division or proliferation of abnormal cells in the body.
- Cancers that can be treated with the methods and the compositions described herein include, but are not limited to, prostate cancer, breast cancer, adrenal cancer, leukemia, lymphoma, myeloma, Waldenstrom's macro globulinemia, monoclonal gammopathy, benign monoclonal gammopathy, heavy chain disease, bone and connective tissue sarcoma, brain tumors, thyroid cancer, pancreatic cancer, pituitary cancer, eye cancer, vaginal cancer, vulvar cancer, cervical cancer, uterine cancer, ovarian cancer, esophageal cancer, stomach cancer, colon cancer, rectal cancer, liver cancer, gallbladder cancer, cholangiocarcinoma, lung cancer, testicular cancer, penal cancer, hepatocellular cancer, oral cancer, skin cancer, kidney cancers, Wilms' tumor and bladder cancer.
- the terms “treat,” “treating” and “treatment” include the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the minimization or delay of the spread of cancer.
- the term “patient” means an animal, including but not limited to an animal such as a human, monkey, cow, horse, sheep, pig, chicken, turkey, quail, cat, dog, mouse, rat, rabbit, or guinea pig. In one embodiment, the patient is a mammal and in another embodiment the patient is a human. In certain embodiments, the patient can be an adult male or female.
- the patient is a male of age about 30 years to about 85 years. In other embodiments, the patient is a female of age about 30 years to about 85 years. In a particular embodiment, the patient has or is susceptible to having ⁇ e.g., through genetic or environmental factors) cancer. In a further embodiment, the patient has or is susceptible to having ⁇ e.g., through genetic or environmental factors) a tumor. In other embodiments, the patient can be castrated or non- castrated.
- vitamin D compound refers to vitamin D; metabolites of vitamin D, such as 1 ⁇ S-dihydroxycholecalciferol, as well as derivatives, analogs and pharmaceutically acceptable salts of vitamin D.
- non-hypercalcemic vitamin D compound refers to a vitamin D compound that at least gives rise to reduced incidences or reduced severity of hypercalcemia as compared to the active form of vitamin D.
- non-hypercalcemic vitamin D analog refers to an analog of vitamin D that at least gives rise to reduced incidences or reduced severity of hypercalcemia as compared to the active form of vitamin D.
- pulse administration of a vitamin D compound or “pulse dosing of a vitamin D compound” refers to a dosing regimen of a vitamin D compound that is interrupted by periods of non-dosing such that the dosing regimen allows the vitamin D compound to have a therapeutic effect while avoiding incidences hypercalcemia.
- the periods of non-dosing can be from three days to one month.
- a pulse administration dosing regimen can include a single dose administration of a vitamin D compound followed by three weeks of non-administration of a vitamin D compound.
- anti-cancer agent refers to any therapeutic agent that directly or indirectly kills cancer cells or directly or indirectly prohibits stops or reduces the proliferation of cancer cells.
- anti-cancer agent refers to an inhibitor of 17 ⁇ -hydroxylase/C 17 , 20 -lyase, (which is an enzyme in testosterone synthesis), an analog thereof, derivative thereof, metabolite thereof or pharmaceutically acceptable salt thereof.
- reference to a particular 17 ⁇ -hydroxylase/Ci 7 ,2o- lyase inhibitor can include analogs, derivatives, metabolites or pharmaceutically acceptable salts of such particular 17 ⁇ -hydroxylase/C
- the phrase "therapeutically effective amount" when used in connection with a vitamin D compound or therapeutic agent means an amount of the vitamin D compound or therapeutic agent effective for treating a disease or disorder disclosed herein, such as cancer.
- refractory cancer means cancer that is not responding to an anti -cancer treatment or cancer that is not responding sufficiently to an anti-cancer treatment.
- Refractory cancer can also include recurring or relapsing cancer.
- refractory patient means a patient who has refractory cancer.
- relapse cancer means cancer that was at one time responsive to an anti-cancer treatment but has become no longer responsive to such treatment or is no longer responding sufficiently to such treatment.
- recurring cancer means cancer that has returned after a patient has been earlier diagnosed with cancer, under gone treatment or had been previously diagnosed as cancer-free.
- derivative refers to a chemically modified compound wherein the chemical modification takes place at one or more functional groups of the compound. The derivative may retain or improve the pharmacological activity of the compound from which it is derived.
- analog refers to a chemical compound that is structurally similar to another but differs slightly in composition (as in the replacement of one atom by an atom of a different element or in the presence of a particular functional group).
- pharmaceutically acceptable salt refers to any salt of a chemical compound that retains the biological effectiveness of the compound.
- pharmaceutically acceptable salts include, but are not limited to, acetates, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-l ⁇ -dioates, hexyne-l,6-dioates, benzoates, chlorobenzoates,
- phthalates sulfonates, xylenesulfonates, phylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, gamma-hydroxybutyrates, glycollates, tartarates, alkanesulfonates ⁇ e.g. methane-sulfonate or mesylate), propanesulfonates, naphthalene- 1 -sulfonates, naphthalene-2-sulfonates, and mandelates.
- Several of the officially approved salts are listed in Remington: The Science and Practice of Pharmacy, Mack Publ. Co., Easton.
- the methods described herein for treating cancer comprise administering to a mammal, preferably a human, a vitamin D compound, such as seocalcitol, in addition to at least one therapeutic agent, such as an anti-cancer agent or a steroid, particularly a corticosteroid or a glucocorticoid.
- a vitamin D compound such as seocalcitol
- the compositions described herein comprise a vitamin D compound and at least one additional therapeutic agent, such as an anti-cancer agent or a steroid, particularly a glucocorticoid.
- Other anti-cancer treatments such as, administration of another anti-cancer agent, radiotherapy, chemotherapy, photodynamic therapy, surgery or other immunotherapy, can be used with the methods and compositions.
- Vitamin D is a fat soluble vitamin which is essential as a positive regulator of calcium homeostasis.
- the active form of vitamin D is 1 ⁇ ,25-dihydroxyvitamin D 3 , also known as calcitriol.
- Vitamin D compounds suitable for the methods and compositions include, but are not limited to, vitamin D, calcitriol, l ⁇ -hydroxy derivatives with a 17 side chain greater in length than the cholesterol or ergosterol side chains (see U.S. Patent No. 4,717,721); cyclopentano-vitamin D analogs (see U.S. Patent No.
- vitamin D 3 analogues with alkynyl, alkenyl, and alkanyl side chains see U.S. Patent Nos. 4,866,048 and 5,145,846); trihydroxycalciferol (see U.S. Patent No. 5,120,722); fluoro-cholecalciferol compounds (see U.S. Patent No. 5,547,947); methyl substituted vitamin D (see U.S. Patent No. 5,446,035); 23-oxa-derivatives (see U.S. Patent No. 5,411,949); 19-nor-vitamin D compounds (see U.S. Patent No.
- non-hypercalcemic vitamin D compounds such as non-hypercalcemid vitamin D analogs.
- non-hypercalcemic vitamin D compounds have the structure of formula (I):
- n 2 or 3
- m is O or an integer from 1 to 4
- R 1 and R 2 (which may be the same or different) stand for hydrogen or Ci-C 8 , hydrocarbyl indicating the residue after removal of a hydrogen atom from a straight, branched or cyclic saturated or unsaturated hydrocarbon, or taken together with the carbon bearing the hydroxy!
- R 1 and R 2 can form a saturated or unsaturated C 3 -C 8 carbocyclic ring; in addition, R 1 and/or R 2 and/or one of the m carbons designated by the "*" may be optionally substituted with one or more chlorine or fluorine atom(s); and finally one of the carbons designated “°” may optionally be substituted by one or two Ci-C 2 alkyl group(s); and derivatives of the compounds of formula (1) in which one or more hydroxy have been transformed into -O-acyl or -O- glycosyl or phosphate ester groups; such masked groups being hydrolyzable in vivo; and other prodrugs thereof.
- the formula (I) and compounds of formula (I) were disclosed in United States Patent No. 5,190,935 to Binderup et al., herein incorporated by reference in its entirety.
- X is hydrogen or hydroxy
- R 1 and R 2 stand for methyl or ethyl (in which R 1 and R 2 can be the same or different);
- Q is methylene, ethylene, tri- or tetra-methylene and may optionally be substituted with an oxy group, -OR 3 , in which R 3 is hydrogen, methyl or ethyl;
- Y is either a single bond or Ci-C 2 hydrocarbylene where hydrocarbylene is the diradical obtained after removal of two hydrogen atoms from a straight, branched or cyclic, saturated or unsaturated hydrocarbon and R 1 .
- R 2 or Y is unsubstituted or substituted by one or more fluorine atoms or a hydroxy 1 group.
- the vitamin D compound is the non- hypercalcemic vitamin D analog, seocalcitol or l(S),3(R)-dihydroxy-20(R)-(5'-ethyl-5'- hydroxyhepta- 1 ' (E),3 ' (E)-dien- 1 ' -yl)-9, 10-secopregna-5 (Z),7(E),- 10(19)-triene which has the following structural formula:
- Seocalcitol has displayed strong antiproliferative activity, low calcemic activity and a biological half-life suitable for systematic use. Seocalcitol has been found to be 50-200 times more potent in regulation of cell growth and differentiation than l ⁇ ,25- dihydroxycholecalciferol in vitro and in vivo, however, its calcemic activity was approximately 50% weaker than that of la,25-dihydroxycholecalciferol in vivo.
- Non-hypercalcemic vitamin D compounds can be made according to any method known to one skilled in the art.
- the therapeutically effective amount of the vitamin D compound administered to a mammal having cancer is an amount that is sufficient to treat the cancer, whether the vitamin D compound is administered alone or in combination with an additional anti-cancer treatment, such as an additional anti-cancer agent.
- Suitable compounds that can be used in addition to a vitamin D compound as an anti-cancer agent include, but are not limited to, hormone ablation agents, anti-androgen agents, differentiating agents, anti-neoplastic agents, kinase inhibitors, anti-metabolite agents, alkylating agents, antibiotic agents, immunological agents, interferon-type agents, intercalating agents, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, mitotic inhibitors, matrix metalloprotease inhibitors, genetic therapeutics, testosterone synthesis inhibitors, and anti-androgens.
- the amount of the additional anti-cancer agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- the examples are not all inclusive and are for purposes of illustration and not for purposes of limitation. Many of the examples below could be listed in multiple classes of anti-cancer agents and are not restricted in any way to the class in which they are listed in.
- Suitable hormonal ablation agents include, but are not limited to, androgen ablation agents and estrogen ablation agents.
- the vitamin D compound is administered with a hormonal ablation agent, such as deslorelin, leuprolide, goserelin, 17 ⁇ hydroxylase/Ci 7 , 2 0 -lyase inhibitor, such as abiraterone acetate (i.e. 3 ⁇ - acetoxy-17-(3-pyridyl) androsta-5, 16-diene) (see e.g., U.S. Patent No. 5,604,213 to Barrie et ⁇ /.), or triptorelin.
- a hormonal ablation agent such as deslorelin, leuprolide, goserelin, 17 ⁇ hydroxylase/Ci 7 , 2 0 -lyase inhibitor, such as abiraterone acetate (i.e. 3 ⁇ - acetoxy-17-(3-pyridyl) androsta-5, 16-
- hormonal ablation agent is written as a singular noun, for example; "a hormonal ablation agent” or “the hormonal ablation agent,” the phrase “hormonal ablation agent” should not be interpreted as being limited to the inclusion of a single hormonal ablation agent.
- the amount of the hormonal ablation agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- Suitable anti-androgen agents include but are not limited to bicalutamide, flutamide and nilutamide.
- the amount of the anti-androgen agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- the vitamin D compound may be administered with a differentiating agent.
- suitable differentiating agents include, but are not limited to, polyamine inhibitors; additional vitamin D compounds; metabolites of vitamin A, such as, ATRA, retinoic acid, retinoids; short-chain fatty acids; phenylbutyrate; and nonsteroidal anti-inflammatory agents.
- the amount of the differentiating agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- the vitamin D compound may be administered with an anti-neoplastic agent, including, but not limited to, tubulin interacting agents, topoisomerase inhibitors and agents, acitretin, alstonine, amonaf ⁇ de, amphethinile, amsacrine, ankinomycin, anti-neoplaston, aphidicolin glycinate, asparaginase, baccharin, batracylin, benfluron, benzotript, bromofosfamide, caracemide, carmethizole hydrochloride, chlorsulfaquinoxalone, clanfenur, claviridenone, crisnatol, curaderm, cytarabine, cytocytin, dacarbazine, datelliptinium, dihaematoporphyrin ether, dihydrolenperone, dinaline, distamycin, docetaxel, ellipra
- the amount of the anti-neoplastic agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- the vitamin D compound may also be used with a kinase inhibitor including p38 inhibitors and CDK inhibitors, TNF inhibitors, metallomatrix proteases inhibitors (MMP), COX-2 inhibitors including celecoxib, rofecoxib, parecoxib, valdecoxib, and etoricoxib, SOD mimics or ⁇ v ⁇ 3 inhibitors.
- the amount of the kinase inhibitor administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- vitamin D compound may be administered with an anti-metabolite agent.
- Suitable anti-metabolite agents may be selected from, but not limited to, 5-FU-fibrinogen, acanthifolic acid, aminothiadiazole, brequinar sodium, carmofur, cyclopentyl cytosine, cytarabine phosphate stearate, cytarabine conjugates, dezaguanine, dideoxycytidine, dideoxyguanosine, didox, doxifluridine, camrabine, floxuridine, fludarabine phosphate, 5-fluorouracil, N-(2'-furanidyl)-5-fluorouracil, isopropyl pyrrolizine, methobenzaprim, methotrexate, norspermidine, pentostatin, piritrexim, plicamycin, thioguanine, tiazofurin, trimetrexate,
- the vitamin D compound may be administered with an alkylating agent.
- Suitable alkylating agents may be selected from, but not limited to, aldo-phosphamide analogues, altretamine, anaxirone, bestrabucil, budotitane, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyplatate, diphenylspiromustine, diplatinum cytostatic, elmustine, estramustine phosphate sodium, fotemustine, hepsul-fam, ifosfamide, iproplatin, lomustine, mafosfamide, mitolactol, oxaliplatin, prednimustine, ranimustine, semustine, spiromustine, tauromustine, temozolomide, teroxirone, tetraplatin and trimelamol.
- the vitamin D compound may be administered with an antibiotic agent.
- antibiotic agents may be selected from, but not limited to, aclarubicin, actinomycin D, actinoplanone, adriamycin, aeroplysinin derivative, amrubicin, anthracycline, azino-mycin-A, bisucaberin, bleomycin sulfate, bryostatin-1, calichemycin, chromoximycin, dactinomycin, daunorubicin, ditrisarubicin B, dexamethasone, doxorubicin, doxorubicin-fibrinogen, elsamicin-A, epirubicin, erbstatin, esorubicin, esperamicin-Al, esperamicin-Alb, fostriecin, glidobactin, gregatin-A, grincamycin, herbimycin, corticosteroids such as
- the amount of the antibiotic agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- the vitamin D compound may also be used with other anticancer agents, including but not limited to, acemannan, aclarubicin, aldesleukin, alemtuzumab, alitretinoin, altretamine, amifostine.
- the vitamin D compound may be administered in combination with an anti-hypercalcemic agent and an additional anti-cancer agent.
- Suitable anti-hypercaicemic agents include, but are not limited to, bisphosphonates, such as pamidronate. etidronate, alendronate, tiludronate, risedronate, zoledronic acid, clodronate, and bisphosphonate EB 1053.
- Suitable anti-cancer agents include, but are not limited to, those anti-cancer agents discussed above.
- the amount of the anti-hypercalcemic agent and anti-cancer agent administered to a mammal having cancer is an amount that is sufficient to treat the vitamin D-induced hypercalcemia and the cancer, respectively, whether administered alone or in combination with a vitamin D compound.
- the vitamin D compound may also be administered or combined with steroids, such as corticosteroids or glucocorticoids.
- the vitamin D compound and the steroid may be administered in the same or in different compositions.
- suitable steroids include hydrocortisone, prednisone, dexamethasone.
- the amount of the steroid administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a vitamin D compound.
- compositions comprising both seocalcitol and a steroid particularly a corticosteroid, or more particularly a glucocorticoid.
- Steroids within the scope of the disclosure include, but are not limited to, (1) hydrocortisone (Cortisol; cyprionate (e.g., CORTEF), oral; sodium phosphate injection (HYDROCORTONE PHOSPHATE); sodium succinate (e.g., A-HYDROCORT, SoIu- CORTEF); cortisone acetate oral or injection forms, etc.), (2) dexamethasone (e.g., Decadron, oral; Decadron-LA injection, etc.), (3) prednisolone (e.g., Delta-CORTEF, prednisolone acetate (ECONOPRED), prednisolone sodium phosphate (HYDELTRAS OL), prednisolone tebutate (HYD
- single unit solid oral dosage forms which comprise an amount from about 0.1 ⁇ g to about 500 ⁇ g of seocalcitol and an amount from about 0.5 mg to about 3.0 mg of a steroid, e.g., glucocorticoid in a single composition, optionally with excipients, carriers, diluents, etc. is contemplated.
- the single unit dosage form can comprise about 0.1 ⁇ g to about 500 ⁇ g of seocalcitol and about 1.0 mg, 1.25 mg, 1.5 mg, or 2.0 mg of a steroid, such as but not limited to corticosteroids or glucocorticoids.
- the vitamin D compound and the additional therapeutic agent can be administered by any method known to one skilled in the art.
- the vitamin D compound and the additional therapeutic agent can be in separate compositions prior to administration.
- the vitamin D compound and the additional therapeutic agent can be combined into a single composition for administration.
- the vitamin D compound and the additional therapeutic agent can be administered sequentially or simultaneously. If administered sequentially, the order of administration is flexible. For instance, a vitamin D compound can be administered prior to administration of the additional therapeutic agent. Alternatively, administration of the additional therapeutic agent can precede administration of a vitamin D compound.
- the vitamin D compound is administered by pulse administration or dosing.
- a pulse administration dosing regimen can include a single dose administration of a vitamin D compound followed by one week of non-administration of a vitamin D compound.
- a pulse administration dosing regimen can include a single dose administration of a vitamin D compound followed by three weeks of non-administration of a vitamin D compound.
- a pulse administration dosing regimen can include a single dose administration of a vitamin D compound followed by one month of non-administration of a vitamin D compound.
- each composition is preferably pharmaceutically suitable for administration.
- the vitamin D compound and the additional therapeutic agent if administered separately, can be administered by the same or different modes of administration.
- modes of administration include parenteral (e.g., subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, intradermal, intraperitoneal, intraportal, intra-arterial, intrathecal, transmucosal, intra-articular, and intrapleural,), transdermal (e.g., topical), epidural, and mucosal (e.g., intranasal) injection or infusion, as well as oral, inhalation, pulmonary, and rectal administration. In specific embodiments, both are oral.
- the vitamin D compound can be administered transdermally and the additional therapeutic agent can be administered parenterally.
- the vitamin D compound can be administered orally, such as in a tablet, caplet or capsule, while the additional therapeutic agent can be administered intravenously.
- intravenous administered therapeutic agents include, but are not limited to, docetaxel injections, such as Taxotere ® ; paclitaxel injections, such as Paclitaxel ® and mitoxantrone injections, such as Novantrone ® .
- the additional therapeutic agent can be in the form of depots or implants such as leuprolide depots and implants, e.g. Viadur ® and Lupron Depot ; triptorelin depots, e.g.
- the suitable daily dosage of the vitamin D compound depends upon a number of factors, including, the nature of the severity of the condition to be treated, the particular inhibitor, the route of administration and the age, weight, and response of the individual patient.
- Suitable daily dosages of vitamin D compound can generally range from about 0.000001 ⁇ g/kg/day to about 125 ⁇ g/kg/day, or from about 0.00001 ⁇ g/kg/day to about 40 ⁇ g/kg/day, or from about 0.0001 ⁇ g/kg/day to about 20 ⁇ g/kg/day, or from about 0.001 ⁇ g/kg/day to about 15 ⁇ g/kg/day in single or multiple doses.
- the vitamin D compound can be administered in an amount from about 0.0001 ⁇ g/day to about 2,500 ⁇ g/day. In certain embodiments, the vitamin D compound can be administered in an amount from about 0.001 ⁇ g/day to about 1,000 ⁇ g/day or from about 0.01 ⁇ g/day to about 750 ⁇ g/day or from about 0.1 ⁇ g/day to about 500 ⁇ g/day in single or multiple doses. In certain embodiments, seocalcitol is administered in single or multiple doses in an amount of about 50 ⁇ ig/day or about 100 ⁇ g/day.
- the vitamin D compound such as seocalcitol
- an additional anti-cancer agent such as mitoxantrone, paclitaxel or docetaxel.
- a method for the treatment of a cancer in a mammal comprises administering an amount of seocalcitol and an amount of mitoxantrone.
- the seocalcitol can be administered in an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day
- the mitoxantrone can be administered in an amount of about 0.1 mg/m 2 to about 20 mg/m 2 .
- the mitoxantrone is administered over a period of between about 10 to about 20 minutes once every 21 days.
- a method for the treatment of a cancer in a mammal can comprise administering an amount of seocalcitol and an amount of paclitaxel.
- the seocalcitol can be administered in an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day
- the paclitaxel can be administered in the amount of about 1 mg/m 2 to about 175 mg/m 2 .
- the paclitaxel is administered over a period of between about 2 to about 5 hours once every three months.
- a method for the treatment of a cancer in a mammal comprises administering an amount of seocalcitol and an amount of docetaxel.
- the seocalcitol can be administered in an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day
- the docetaxel can be administered in an amount of about 1 mg/m 2 to about 100 mg/m 2 .
- the docetaxel is administered over a period of between about 1 to about 2 hours once every three weeks.
- the vitamin D compound such as seocalcitol
- an anti-cancer agent that comprises a hormonal ablation agent, including, but not limited to, leuprolide, goserelin, or triptorelin.
- an anti-cancer agent that comprises a hormonal ablation agent, including, but not limited to, leuprolide, goserelin, or triptorelin.
- one method for the treatment of a cancer in a mammal also comprises administering an amount of seocalcitol and an amount of leuprolide.
- the amount of seocalcitol can be about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day, and the amount of leuprolide can be about 0.01 mg to about 200 mg over a period of about 3 days to about 12 months.
- the leuprolide is administered in the amount of about 3.6 mg of leuprolide over a period of about 3 days to about 12 months.
- the methods for the treatment of cancer in a mammal include administering an amount of seocalcitol and an amount of goserelin.
- the amount of seocalcitol can be about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day
- the amount of goserelin can be about 0.01 mg to about 20 mg over a period of about 28 days to about 3 months.
- the goserelin is administered in the amount of about 3.6 mg to about 10.8 mg over a period of about 28 days to about 3 months.
- the methods for the treatment of cancer in a mammal comprise administering an amount of seocalcitol and an amount of triptorelin.
- the amount of seocalcitol can be about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day
- the amount of triptorelin can be about 0.01 mg to about 20 mg, over a period of about 1 month, preferably, the triptorelin is administered in the amount of about 3.75 mg over a period of about 1 month.
- the method for the treatment of a cancer in a mammal comprises administering an amount of seocalcitol and an amount of abiraterone acetate.
- the method involves administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day of seocalcitol, and an amount of about 0.4 mg/day to about 10,000 mg/day of abiraterone acetate.
- the method for the treatment of a cancer in a mammal comprises administering an amount of seocalcitol and an amount of bicalutamide.
- the method involves administering an amount of seocalcitol can be about 0.1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day, and an amount of about 1 mg/day to about 300 mg/day of bicalutamide.
- the method for the treatment of a cancer in a mammal comprises administering an amount of seocalcitol and an amount of flutamide.
- the method comprises administering an amount of seocalcitol can be about 0-1 ⁇ g/day to about 500 ⁇ g/day, such as about 100 ⁇ g/day, and an amount of about 1 mg/day to about 2000 mg/day of flutamide.
- the method for the treatment of a cancer in a mammal can comprise administering an amount of a vitamin D compound and an amount of a glucocorticoid, including but not limited to hydrocortisone, prednisone or dexamethasone.
- the method can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day, and an amount of about 0.01 mg/day to about 500 mg/day of hydrocortisone.
- the method can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol and an amount of about 10 mg/day to about 250 mg/day of hydrocortisone.
- the method for the treatment of a cancer can also comprise administering an amount of a vitamin D compound and an amount of a glucocorticoid, such as prednisone.
- the method can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day, and an amount of about 0.01 mg/day to about 500 mg/day of prednisone.
- the method can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol and an amount of about 10 mg/day to about 250 mg/day of prednisone.
- the method for the treatment of a cancer can also comprise administering an amount of a vitamin D compound and an amount of a glucocorticoid, such as dexamethasone.
- the method can comprise administering an amount of about 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol, such as about 100 ⁇ g/day, and an amount of about 0.01 mg/day to about 500 mg/day of dexamethasone.
- the method can comprise administering an amount of 0.1 ⁇ g/day to about 500 ⁇ g/day of seocalcitol and an amount of about 0.5 mg/day to about 25 mg/day of dexamethasone.
- the method for the treatment of a cancer in a mammal comprises pulse administering an amount of seocalcitol in combination with a chemotherapy treatment.
- Compositions Comprising a Vitamin D Compound and an Additional Therapeutic Agent
- the compositions can contain a combination of a vitamin D compound, preferably seocalcitol, and any of the therapeutic agents recited above. Whether the vitamin D compound and the additional therapeutic agent are administered in separate compositions or as a single composition, the compositions can take various forms. For example, the compositions can take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders or sustained-release formulations, depending on the intended route of administration.
- compositions can be formulated as solutions, gels, ointments, creams, suspensions or salves.
- compositions may be formulated as tablets, pills, dragees, troches, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.
- compositions may also be formulated in rectal or vaginal compositions such as suppositories or retention enemas that contain conventional suppository bases such as cocoa butter or other glycerides.
- the composition may also be formulated as a depot preparation.
- Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection.
- the therapeutic agents may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
- the composition may be delivered using a sustained-release system, such as semi-permeable matrices of solid polymers containing the composition.
- sustained-release system such as semi-permeable matrices of solid polymers containing the composition.
- sustained-release materials have been established and are well known by those skilled in the art.
- Sustained-release capsules may, depending on their chemical nature can release the composition over a period of hours, days, weeks, months. For example, a sustained release capsule can release the compositions over a period of 100 days or longer.
- additional strategies for stabilization may be employed.
- the compositions can further comprise a pharmaceutically acceptable carrier.
- the term “carrier” refers to a diluent, adjuvant (e.g., Freund's adjuvant (complete and incomplete)), excipient, or vehicle with which the therapeutic is administered.
- the composition can comprise one or more of the following carriers: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerin, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose.
- the parenteral preparation can be enclosed in ampules, disposable syringes or multiple dose vials made of glass or plastic.
- suitable carriers include fillers such as sugars, e.g., lactose, sucrose, mannitol and sorbitol; cellulose preparations such as maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, fats and oils; granulating agents; and binding agents such as microcrystalline cellulose, gum tragacanth or gelatin; disintegrating agents, such as cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate, Primogel, or corn starch; lubricants, such as magnesium stearate or Sterotes; glidants, such as colloidal silicon dioxide; a sweetening agent, such as sucrose or saccharin; or flavoring agents, such as peppermint, methyl salicylate, or orange flavoring.
- fillers such as sugars, e.g., lacto
- solid dosage forms may be sugar-coated or enteric-coated using standard techniques.
- suitable oral formulations include lipid- containing formulations, such as, but not limited to, medium chain triglyceride and long chain triglyceride.
- the lipid formulations have been shown to have a positive effect on the solubilization process resulting in a twofold higher bioavailability of seocalcitol compared with a formulation containing propylene glycol. Examples of methods of making suitable lipid formulations are disclosed in Journal of Pharmaceutical Sciences, 94, 1830-1838, 2005, herein incorporated by reference.
- suitable carriers include physiological saline, bacteriostatic water, phosphate buffered saline (PBS).
- PBS phosphate buffered saline
- the composition must be sterile and should be fluid to the extent that easy injectability with a syringe. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi.
- the carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof.
- the proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants.
- Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like.
- isotonic agents for example, sugars; polyalcohols such as mannitol, sorbitol; sodium chloride in the composition.
- Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.
- compositions may be formulated in solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer.
- physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer.
- the solution may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
- the compositions are formulated in sterile solutions.
- penetrants appropriate to the barrier to be permeated are used in the formulation.
- penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives.
- Transmucosal administration can be accomplished through the use of nasal sprays or suppositories.
- the compositions may be formulated as an aerosol spray from pressurized packs or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas.
- a suitable propellant e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas.
- the dosage unit may be determined by providing a valve to deliver a metered amount.
- Capsules and cartridges of gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the composition and a suitable powder base such as lactose or starch.
- the pharmaceutical compositions may be manufactured by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying
- compositions comprising a vitamin D compound and an additional therapeutic agent
- an oral composition or composition suitable for oral administration comprising seocalcitol in combination with a steroid.
- the oral composition can be a solid dosage form, such as a pill, a tablet or a capsule.
- the oral composition can comprise about 0.0001 ⁇ g, 0.001 ⁇ g, 0.01 ⁇ g, 0.05 ⁇ g, 0.1 ⁇ g, 0.25 ⁇ g, 0.5 ⁇ g, 0.75 ⁇ g, 1.0 ⁇ g, 2.5 ⁇ g 5 5.0 ⁇ g, 7.5 ⁇ g, 10 ⁇ g, 25 ⁇ g, 50 ⁇ g, 75 ⁇ g, 100 ⁇ g, 150 ⁇ g, 200 ⁇ g, 250 ⁇ g, 300 ⁇ g, 350 ⁇ g, 400 ⁇ g, 450 ⁇ g, 500 ⁇ g, 550 ⁇ g, 600 ⁇ g, 650 ⁇ g, 700 ⁇ g, 750 ⁇ g, 800 ⁇ g, 850 ⁇ g, 900 ⁇ g, 950 ⁇ g, or 1000 ⁇ g of seocalcitol.
- the oral composition can comprises about 0.25 mg, 0.5 mg, 0.75 mg, 1.0 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, 4.0 mg, 4.25 mg, 4.5 mg, 4.75 mg, 5.0 mg, 7.5 mg, 10 mg, 20 mg, 30 mg, 40 mg or 50 mg of a steroid.
- the oral composition can comprise about 0.1 ⁇ g to about
- composition can comprise about 0.1 ⁇ g to about 500 ⁇ g of seocalcitol and an amount of about 1.0 mg to about 2.5 mg of the steroid, such as hydrocortisone, prednisone or dexamethasone.
- the description contained herein is for purposes of illustration and not for purposes of limitation.
- the methods and compositions described herein can comprise any feature described herein either alone or in combination with any other feature(s) described herein. Changes and modifications may be made to the embodiments of the description. Furthermore, obvious changes, modifications or variations will occur to those skilled in the art. Also, all references cited above are incorporated herein, in their entirety, for all purposes related to this disclosure.
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Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11175046.9A EP2425874A3 (de) | 2006-08-25 | 2007-08-23 | Verwendung von einer Vitamin D Verbindung und eines zusätzlichen therapeutischen Mittel in der Behandlung von Krebs |
Applications Claiming Priority (2)
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US93492406P | 2006-08-25 | 2006-08-25 | |
PCT/US2007/018770 WO2008024485A2 (en) | 2006-08-25 | 2007-08-23 | Methods for treating cancer comprising the administration of a vitamin d compound and an additional therapeutic agent |
Publications (1)
Publication Number | Publication Date |
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EP2063963A2 true EP2063963A2 (de) | 2009-06-03 |
Family
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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EP07837327A Withdrawn EP2063963A2 (de) | 2006-08-25 | 2007-08-23 | Verfahren zur krebsbehandlung mit verabreichung einer vitamin-d-verbindung und eines zusätzlichen therapeutischen mittels |
EP11175046.9A Withdrawn EP2425874A3 (de) | 2006-08-25 | 2007-08-23 | Verwendung von einer Vitamin D Verbindung und eines zusätzlichen therapeutischen Mittel in der Behandlung von Krebs |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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EP11175046.9A Withdrawn EP2425874A3 (de) | 2006-08-25 | 2007-08-23 | Verwendung von einer Vitamin D Verbindung und eines zusätzlichen therapeutischen Mittel in der Behandlung von Krebs |
Country Status (9)
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EP (2) | EP2063963A2 (de) |
JP (1) | JP2010501576A (de) |
KR (1) | KR20090060306A (de) |
CN (1) | CN101528309A (de) |
AU (1) | AU2007287099A1 (de) |
CA (2) | CA2661546A1 (de) |
IL (1) | IL197212A0 (de) |
NO (1) | NO20091191L (de) |
WO (1) | WO2008024485A2 (de) |
Families Citing this family (14)
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SG173119A1 (en) * | 2009-01-27 | 2011-08-29 | Berg Biosystems Llc | Vitamin d3 and analogs thereof for alleviating side effects associated with chemotherapy |
ES2475945T3 (es) | 2009-06-26 | 2014-07-11 | Novartis Ag | Derivados imidazolidin-2 -ona 1,3-disustituida como inhibidores de CYP 17 |
ES2426098T3 (es) * | 2009-07-16 | 2013-10-21 | Institut National de la Santé et de la Recherche Médicale | Composiciones farmacéuticas y su uso en el tratamiento del cáncer |
WO2012035078A1 (en) | 2010-09-16 | 2012-03-22 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
US20120116381A1 (en) | 2010-11-05 | 2012-05-10 | Houser Kevin L | Surgical instrument with charging station and wireless communication |
CA2834224A1 (en) | 2011-04-28 | 2012-11-01 | Novartis Ag | 17.alpha.-hydroxylase/c17,20-lyase inhibitors |
US9801844B2 (en) * | 2012-05-24 | 2017-10-31 | The Research Foundation Of The City University Of New York | Methods and compositions for the treatment of cancer |
ES2836424T3 (es) | 2012-09-26 | 2021-06-25 | Aragon Pharmaceuticals Inc | Antiandrógenos para tratar el cáncer de próstata no metastásico y resistente a la castración |
WO2014058785A1 (en) | 2012-10-10 | 2014-04-17 | Novartis Ag | Combination therapy |
JOP20200097A1 (ar) * | 2013-01-15 | 2017-06-16 | Aragon Pharmaceuticals Inc | معدل مستقبل أندروجين واستخداماته |
WO2014176394A1 (en) | 2013-04-24 | 2014-10-30 | Salk Institute For Biological Studies | Vitamin d receptor/smad genomic circuit gates fibrotic response |
WO2014197680A1 (en) | 2013-06-05 | 2014-12-11 | Salk Institute For Biological Studies | Vitamin d receptor agonists to treat diseases involving cxcl12 activity |
WO2019023149A1 (en) | 2017-07-24 | 2019-01-31 | Salk Institute For Biological Studies | USE OF BROMODOMAIN-CONTAINING PROTEIN-9 ANTAGONISTS IN ASSOCIATION WITH VITAMIN D RECEPTOR AGONISTS IN THE TREATMENT OF DIABETES |
KR20200070334A (ko) | 2017-10-16 | 2020-06-17 | 아라곤 파마슈티컬스, 인코포레이티드 | 비-전이성 거세-저항성 전립선암의 치료를 위한 항-안드로겐 |
Citations (1)
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WO2001064251A2 (en) * | 2000-03-02 | 2001-09-07 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Combination chemotherapy |
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US5120722A (en) | 1984-02-08 | 1992-06-09 | Hoffmann-La Roche Inc. | Trihydroxy-cholecacliferol and trihydroxy-ergocalciferol for treating leukemia |
US4857518A (en) | 1984-10-04 | 1989-08-15 | Wisconsin Alumni Research Foundation | Hydroxylated 24-homo-vitamin D derivatives and methods for preparing same |
US4717721A (en) | 1985-05-30 | 1988-01-05 | Howard W. Bremer | Sidechain homo-vitamin D compounds with preferential anti-cancer activity |
DE3666587D1 (en) | 1985-08-02 | 1989-11-30 | Leo Pharm Prod Ltd | Novel vitamin d analogues |
US5145846A (en) | 1988-01-20 | 1992-09-08 | Hoffmann-La Roche Inc. | Vitamin D3 analogs |
US4851401A (en) | 1988-07-14 | 1989-07-25 | Wisconsin Alumni Research Foundation | Novel cyclopentano-vitamin D analogs |
CA1333616C (en) | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
GB8915770D0 (en) | 1989-07-10 | 1989-08-31 | Leo Pharm Prod Ltd | Chemical compounds |
DE4101953A1 (de) | 1991-01-19 | 1992-07-23 | Schering Ag | 23-oxa-derivate in der vitamin-d-reihe, verfahren zu ihrer herstellung diese derivate enthaltende pharmazeutische praeparate sowie deren verwendung als arzneimittel |
DE4141746A1 (de) | 1991-12-13 | 1993-06-17 | Schering Ag | 20-methyl-substituierte vitamin d-derivate |
US5604213A (en) | 1992-03-31 | 1997-02-18 | British Technology Group Limited | 17-substituted steroids useful in cancer treatment |
US5547947A (en) | 1993-03-11 | 1996-08-20 | Hoffmann-La Roche Inc. | Methods of treatment |
GB9622590D0 (en) | 1996-10-30 | 1997-01-08 | Leo Pharm Prod Ltd | Chemical compounds |
US6521608B1 (en) | 1998-03-27 | 2003-02-18 | Oregon Health & Science University | Vitamin D and its analogs in the treatment of tumors and other hyperproliferative disorders |
US7094775B2 (en) * | 2004-06-30 | 2006-08-22 | Bone Care International, Llc | Method of treating breast cancer using a combination of vitamin D analogues and other agents |
-
2007
- 2007-08-23 EP EP07837327A patent/EP2063963A2/de not_active Withdrawn
- 2007-08-23 KR KR1020097005973A patent/KR20090060306A/ko not_active Application Discontinuation
- 2007-08-23 CN CNA2007800385939A patent/CN101528309A/zh active Pending
- 2007-08-23 WO PCT/US2007/018770 patent/WO2008024485A2/en active Application Filing
- 2007-08-23 CA CA002661546A patent/CA2661546A1/en not_active Abandoned
- 2007-08-23 JP JP2009525648A patent/JP2010501576A/ja active Pending
- 2007-08-23 CA CA2838089A patent/CA2838089A1/en not_active Abandoned
- 2007-08-23 AU AU2007287099A patent/AU2007287099A1/en not_active Abandoned
- 2007-08-23 EP EP11175046.9A patent/EP2425874A3/de not_active Withdrawn
-
2009
- 2009-02-24 IL IL197212A patent/IL197212A0/en unknown
- 2009-03-20 NO NO20091191A patent/NO20091191L/no not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001064251A2 (en) * | 2000-03-02 | 2001-09-07 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Combination chemotherapy |
Non-Patent Citations (1)
Title |
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O'DONNELL A ET AL: "Hormonal impact of the 17[alpha]-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer", BRITISH JOURNAL OF CANCER, NATURE PUBLISHING GROUP, GB, vol. 90, no. 12, 14 June 2004 (2004-06-14), pages 2317 - 2325, XP002464868, ISSN: 0007-0920 * |
Also Published As
Publication number | Publication date |
---|---|
WO2008024485A3 (en) | 2009-03-05 |
EP2425874A2 (de) | 2012-03-07 |
CA2838089A1 (en) | 2008-02-28 |
JP2010501576A (ja) | 2010-01-21 |
CA2661546A1 (en) | 2008-02-28 |
NO20091191L (no) | 2009-03-23 |
AU2007287099A1 (en) | 2008-02-28 |
EP2425874A3 (de) | 2013-05-15 |
KR20090060306A (ko) | 2009-06-11 |
IL197212A0 (en) | 2009-12-24 |
CN101528309A (zh) | 2009-09-09 |
WO2008024485A2 (en) | 2008-02-28 |
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