# US 2012/0238532 A1 · Treatment of human osteosarcoma

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- Number: US 2012/0238532 A1
- Document ID: US20120238532A1
- Status: Published application
- Kind: A1
- Application number: 13/512,855
- Filed: 2010-11-30
- Published: 2012-09-20
- Earliest claimed: 2009-11-30
- Assignees: Cedars-Sinai Medical Center
- Inventors: Dhong Hyun Lee; Nils H. Thoennissen; H. Phillip Koeffler
- Web page: https://patentgrep.com/patent/US20120238532A1

## CPC

- A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention describes the combination of cucurbitacin (CuB) with methotrexate (MTX) for the treatment of cancers, including osteosarcoma. It was discovered that CuB and MTX have synergistic activity against osteosarcoma, which reduces toxicities associated with both chemotherapeutic agents. The present invention also describes the use of CuB for the treatment of osteosarcoma.

## Claims

### Claim 1

A method of treating cancer in a mammal, comprising:
administering a quantity of cucurbitacin B (CuB) with a quantity of methotrexate (MTX) to the mammal in need thereof, in an amount effective to treat the cancer,
wherein CuB and/or MTX is a pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the cancer is osteosarcoma.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the administration of the combination of CuB and MTX has a synergistic effect in the treatment of cancer.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the quantity of CuB is administered in a low dose.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the low dose quantity of CuB is administered every one to three days.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the quantity of MTX is administered in a low dose.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the low dose quantity of MTX is administered every one to three weeks.

### Claim 8

A method of inducing apoptosis in cancer cells in a mammal, comprising:
administering a quantity of CuB with a quantity of MTX to the mammal in need thereof, in an amount effective to induce apoptosis of the cancer cells in the mammal,
wherein CuB and/or MTX is a pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the cancer is osteosarcoma.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the administration of the combination of CuB and MTX has a synergistic effect in the treatment of cancer.

### Claim 11 (depends on 8)

The method according to claim 8, wherein the quantity of CuB is administered in a low dose.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the low dose quantity of CuB is administered every one to three days.

### Claim 13 (depends on 8)

The method according to claim 8, wherein the quantity of MTX is administered in a low dose.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the low dose quantity of MTX is administered every one to three weeks.

### Claim 15

A method of preventing metastases of cancer in a mammal, comprising:
administering a quantity of CuB with a quantity of MTX to the mammal in need thereof, in an amount effective to prevent metastases of the cancer in the mammal,
wherein CuB and/or MTX is a pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 16 (depends on 16)

The method according to claim 16, wherein the cancer is osteosarcoma.

### Claim 17 (depends on 17)

The method according to claim 17, wherein the administration of the combination of CuB and MTX has a synergistic effect in the treatment of cancer.

### Claim 18 (depends on 17)

The method according to claim 17, wherein the quantity of CuB is administered in a low dose.

### Claim 19 (depends on 18)

The method according to claim 18, wherein the low dose quantity of CuB is administered every one to three days.

### Claim 20 (depends on 16)

The method according to claim 16, wherein the quantity of MTX is administered in a low dose.

### Claim 21 (depends on 20)

The method according to claim 20, wherein the low dose quantity of MTX is administered every one to three weeks.

### Claim 22

A method of reducing the likelihood metastases of cancer in a mammal, comprising:
administering a quantity of CuB with a quantity of MTX to the mammal in need thereof, in an amount effective to prevent metastases of the cancer in the mammal,
wherein CuB and/or MTX is a pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 23 (depends on 22)

The method according to claim 22, wherein the cancer is osteosarcoma.

### Claim 24 (depends on 22)

The method according to claim 22, wherein the administration of the combination of CuB and MTX has a synergistic effect in the treatment of cancer.

### Claim 25 (depends on 22)

The method according to claim 22, wherein the quantity of CuB is administered in a low dose.

### Claim 26 (depends on 25)

The method according to claim 25, wherein the low dose quantity of CuB is administered every one to three days.

### Claim 27 (depends on 22)

The method according to claim 22, wherein the quantity of MTX is administered in a low dose.

### Claim 28 (depends on 27)

The method according to claim 27, wherein the low dose quantity of MTX is administered every one to three weeks.

### Claim 29

A composition for treating cancer in a mammal, comprising:
a quantity of CuB and a quantity of MTX,
wherein CuB and/or MTX is pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 30

A composition for inducing apoptosis of cancer cells in a mammal, comprising:
a quantity of CuB and a quantity of MTX,
wherein CuB and/or MTX is pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 31

A composition for preventing metastases or reducing the likelihood of metastases of cancer in a mammal, comprising:
a quantity of CuB and a quantity of MTX,
wherein CuB and/or MTX is pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.

### Claim 32

A kit for treating cancer comprising a composition comprising:
a quantity of CuB, a quantity of MTX, and
instructions for use,
wherein CuB and/or MTX is pharmaceutical equivalent, analog, derivative, salt or prodrug thereof.
