Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally

Patent metadata

Field	Value
Publication number	US-9107824-B2
Application number	US-12219108-A
Country	US
Kind code	B2
Filing date	May 16, 2008
Priority date	Nov 8, 2005
Publication date	Aug 18, 2015
Grant date	Aug 18, 2015

Abstract

One aspect of the invention relates to methods of treating cancer in a patient comprising administering intraperitoneally to a patient in need thereof a cancer treating effective amount of a composition comprising a lipid-complexed platinum compound wherein the concentration of the platinum compound of the lipid-complexed platinum compound composition is greater than about 1.2 mg/ml. Another aspect of the invention relates to lipid-complexed platinum compound compositions where the concentration of the platinum compound is greater than about 1.2 mg/ml.

First claim

We claim:

1. A method of treating a cancer, comprising administering intraperitoneally to a patient in need thereof a composition comprising a therapeutic amount of a lipid-complexed active platinum compound aggregate, wherein the lipid component of the lipid-complexed active platinum compound aggregate consists of electrically neutral lipids; and the lipid to active platinum compound weight ratio (L/D) in the lipid-complexed active platinum compound aggregate is from about 0.10 (L/D) to about 0.50 (L/D).

2. The method of claim 1 , wherein the lipid to active platinum compound weight ratio is from about 0.15 (L/D) to about 0.45 (L/D).

3. The method of claim 2 , wherein the lipid to active platinum compound weight ratio is from about 0.20 (L/D) to about 0.40 (L/D).

4. The method of claim 3 , wherein the lipid to active platinum compound weight ratio is about 0.2 (L/D).

5. The method of claim 1 , wherein the lipid-complexed active platinum compound aggregate has an average volume-weighted diameter of about 0.5 to about 20 microns.

6. The method of claim 5 , wherein the average volume-weighted diameter of the lipid-complexed active platinum compound aggregate is about 1 to about 15 microns.

7. The method of claim 5 , wherein the average volume-weighted diameter of the lipid-complexed active platinum compound aggregate is about 2 to 10 microns.

8. The method of claim 1 , wherein the therapeutic amount of the active platinum compound aggregate in the composition ranges from about 1.2 mg/ml to about 20 mg/ml.

9. The method of claim 8 , wherein the therapeutic amount of the active platinum compound aggregate ranges from about 1.5 to about 5 mg/ml.

10. The method of claim 1 , wherein the lipid-complexed active platinum compound contains about 70% to about 100% of total active platinum compound in the composition.

11. The method of claim 10 , wherein the lipid-complexed active platinum compound contains about 75% to about 99% of the total active platinum compound in the composition.

12. The method of claim 11 , wherein the lipid-complexed active platinum compound contains about 80% to about 90% of the total active platinum compound in the composition.

13. The method of claim 1 , wherein the lipid-complexed active platinum compound contains about 0.1% to about 5% of total lipid in the composition.

14. The method of claim 13 , wherein lipid-complexed active platinum compound contains about 0.25% to about 3% of the total lipid in the composition.

15. The method of claim 1 , wherein the active platinum compound is selected from the group consisting of cisplatin, carhoplatin (diammine(1,1-cyclobutanedicarboxylato)-platinum(II)), tetraplatin (ormaplatin) (tetrachloro (1,2-cyclohexanediamine-N,N′)-platinum(IV)), thioplatin (bis(0-ethyldithiocarbonato)platinum(II)), satraplatin, nedaplatin, oxaliplatin, heptaplatin, iproplatin, transplatin, lobaplatin, cis aminedichloro(2-methylpyridine) platinum, JM118 (cis-amminedichloro(cyclohexylamine) platinum(II)), JM 149 (cis-amminedichloro(cyclohexylamine)-trans-dihydroxoplatinurn(IV)), JM216 (bis-acetato-cis-amminedichloro(cyclohexylamine) platinurn(IV)), JM335 (trans-amminedichloro (cyclohexylamine)dihydroxoplatinum(IV)), (trans, trans, trans)bis-mu-(hexane-1,6-diamine)-mu-[diamine-platinurn(II)]bis[diamine(chloro) platinum(II)]tetrachloride, and a mixture thereof.

16. The method of claim 1 , wherein the active platinum compound is cisplatin.

17. The method of claim 1 , wherein the electrically neutral lipids consist of a phosphatidylcholine.

18. The method of claim 17 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).

19. The method of claim 1 , wherein the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and a sterol.

20. The method of claim 19 , wherein the sterol is cholesterol.

21. The method of claim 20 , wherein the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and cholesterol in a ratio of about 1:1 by weight to about 5:1 by weight.

22. The method of claim 21 , wherein the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and cholesterol in a ratio of about 2:1 by weight to about 4:1 by weight.

23. The method of claim 22 , wherein the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and cholesterol in a ratio of about 2.25:1 by weight.

24. The method of claim 1 , wherein the cancer is selected from the group consisting of melanoma, testis (germ cell) cancer, osteosarcoma, soft tissue sarcoma, thyroid cancer, colon cancer, ovarian cancer, cancer of the kidney, breast cancer, colorectal cancer, prostate cancer, bladder cancer, uterine cancer, lung cancer, stomach cancer, liver cancer, spleen cancer, endometrial, and squamous cell carcinomas of the head and neck.

25. The method of claim 1 , wherein the cancer is ovarian cancer.

26. The method of claim 1 , wherein the patient is a human.

27. The method of claim 1 , wherein the composition is administered to the patient at least once every three weeks.

28. The method of claim 1 , wherein the therapeutic amount of the active platinum compound aggregate in the composition is at least 60 milligrams per body surface area (mg/m 2 ).

29. The method of claim 1 , wherein the therapeutic amount of the active platinum compound aggregate in the composition is at least 100 milligrams per body surface area (mg/m 2 ), and the composition is administered to the patient at least once every three weeks.

30. The method according to claim 1 , wherein the therapeutic amount of the active platinum compound aggregate in the composition is at least 140 milligrams per body surface area (mg/m 2 ).

31. The method of claim 1 , wherein the therapeutic amount of the active platinum compound aggregate in the composition is at least 180 milligrams per body surface area (mg/m 2 ).

Assignees

• Pilkiewicz Frank G
• Perez-Soler Roman
• Zou Yiyu
• Perkins Walter R
• Lee Jin K
• Malinin Vladimir
• Insmed Inc

Inventors

• Pilkiewicz Frank G
• Perez-Soler Roman
• Zou Yiyu
• Perkins Walter R
• Lee Jin K
• Malinin Vladimir

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/555

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title