TREATMENT OF HYPERPROLIFERATIVE DISEASES USING HIGH DOSES OF ACTIVE VITAMIN D

• US 20070043005A1
• Filed: 05/11/2006
• Published: 02/22/2007
• Est. Priority Date: 12/30/1996
• Status: Abandoned Application

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Mazess, Richard
• Application Number:
  US11/382,887
• Publication Number:
  US 20070043005A1
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/20 : for decreasing, blocking or antagonising the activity of PTH
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid

Abstract

The present invention provides a method of inhibiting the hyperproliferative cellular activity of neoplasms and other hyperproliferative diseases with an active vitamin D compound utilizing a high dose, episodic treatment protocol.

Claims

1. A method of inhibiting hyperproliferation of malignant or neoplastic cells, comprising treating the cells episodically with an antiproliferative amount of an active vitamin D compound;

the cells expressing a vitamin D receptor, wherein the amount of active vitamin D is a high dose which is between about 10 μ

g to about 200[g/dose given once per week to once every 12 weeks;

wherein the active vitamin D compound is a compound of formula (III);

wherein A¹ and A² each are hydrogen or together represent a carbon-carbon bond, thus forming a double bond between C-22 and C-23;

R¹ and R² are identical or different and are hydrogen, lower alkyl, lower fluoroalkyl, O-lower alkyl, lower alkenyl, lower fluoroalkenyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl, lower cycloalkyl with the proviso that R¹ and R² cannot both be an alkenyl group, or taken together with the carbon to which they are bonded, form a C₃-C₈ cyclocarbon ring;

R³ is lower alkyl, lower alkenyl, lower fluoroalkyl, lower fluoroalkenyl, O-lower alkyl, O-lower alkenyl, O-loweracyl, O-aromatic acyl or lower cycloalkyl;

X¹ is hydrogen or hydroxyl, or, taken with R³, constitutes a bond when R³ is an alkenyl group, and X² is hydrogen or hydroxyl, or, taken with R¹ or R², constitutes a double bond.

2. The method of claim 1, wherein the malignant cells are associated with cancers of the breast, colon, prostate, lung, pancreas, endometrium, liver, squamous cell carcinoma, myeloid leukemia, melanoma, retinoblastoma, sarcomas of the soft tissues or bone.

3. The method of claim 1 wherein the active vitamin D is 1α

-hydroxyvitamin D₂ or 1α

,24-dihydroxyvitamin D₂.

4. The method of claim 3 wherein the active vitamin D is 1α

-hydroxyvitamin D₂.

5. The method of claim 3 wherein the active vitamin D is 1α

,24-dihydroxyvitamin D₂.

6. The method of claim 1 wherein the active vitamin D is 1α

-hydroxyvitamin D₄;

1α

,25-dihydroxyvitamin D₂;

1α

,24,25-trihydroxyvitamin D₂ , 1α

,25-dihydroxyvitamin D₄;

1α

,24,25-trihydroxyvitamin D₄;

24-hydroxyvitamin D₂;

or 24-hydroxyvitamin D₄.

7. The method of claim 1 wherein the active vitamin D is administered to a human cancer patient, the amount of the active vitamin D effective to inhibit the hyperproliferation of the neoplastic cells.

8. The method of claim 1 wherein the active vitamin D compound is administered parenterally or orally in combination with a pharmaceutically acceptable carrier.

9. The method of claim 8 wherein the active vitamin D compound is administered parenterally.

10. The method of claim 9 wherein the active amount of vitamin D compound is administered intravenously.

11. The method of claim 10 wherein the active vitamin D compound is administered orally.