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

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.

We claim: 
     
         1 . A method 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 active platinum compound, wherein the lipid complexed active platinum compound has a lipid to drug (L/D) ratio of less than about 1 by weight. 
     
     
         2 . The method of  claim 1 , wherein the lipid to drug ratio is about 0.10 to about 1 by weight. 
     
     
         3 . The method of  claim 2 , wherein the lipid to drug ratio is about 0.10 to about 0.50 by weight. 
     
     
         4 . The method of  claim 3 , wherein the lipid to drug ratio is about 0.15 to about 0.45 by weight. 
     
     
         5 . The method of  claim 4 , wherein the lipid to drug ratio is about 0.20 to about 0.40 by weight. 
     
     
         6 . The method of  claim 5 , wherein the lipid to drug ratio is about 0.2 by weight. 
     
     
         7 . The method of  claim 1 , wherein lipid-complexed active platinum compound has an average volume-weighted diameter of about 0.5 to about 20 microns. 
     
     
         8 . The method of  claim 6 , wherein the average volume-weighted diameter is about 1 to about 15 microns. 
     
     
         9 . The method of  claim 7 , wherein the average volume-weighted diameter is about 2 to 10 microns. 
     
     
         10 . The method of  claim 1 , wherein the concentration of the active platinum compound in the composition is greater than about 1.2 mg/ml. 
     
     
         11 . The method of  claim 10 , wherein the platinum compound concentration is about 1.2 to about 20 mg/ml. 
     
     
         12 . The method of  claim 12 , wherein the platinum compound concentration is about 1.5 to about 5 mg/ml. 
     
     
         13 . The method of  claim 1 , further comprising a liposome. 
     
     
         14 . The method of  claim 13 , wherein the liposome comprises an active platinum compound. 
     
     
         15 . The method of  claim 14 , wherein the lipid-complexed active platinum compound contains about 70 to about 100% of the total active platinum compound in the composition. 
     
     
         16 . The method of  claim 15 , wherein in the lipid-complexed active platinum compound contains about 75 to about 99% of the total active platinum compound. 
     
     
         17 . The method of  claim 16 , wherein the lipid-complexed active platinum compound contains about 80 to about 90% of the total active platinum compound. 
     
     
         18 . The method of  claim 14 , wherein the liposome contains about 0 to about 30% of the total active platinum compound in the composition. 
     
     
         19 . The method of  claim 18 , wherein the liposome contains about 0.5 to about 25% of the total active platinum compound. 
     
     
         20 . The method of  claim 19 , wherein the liposome contains about 1 to about 20% of the total platinum compound. 
     
     
         21 . The method of  claim 13 , wherein the lipid-complexed active platinum compound contains about 0.1 to about 5% of the total lipid in the composition, 
     
     
         22 . The method of  claim 21 , wherein the lipid-complexed active platinum compound contains about 0.25 to about 3% of the total lipid. 
     
     
         23 . The method of  claim 13 , wherein the liposome contains about 75 to about 99.5% of the total lipid in the composition. 
     
     
         24 . The method of  claim 23 , wherein the liposome contains about 80 to about 95% of the total lipid 
     
     
         25 . The method of  claim 13 , wherein the lipid-complexed active platinum compound has a lipid to platinum compound ratio of about 0.10 to about 0.50. 
     
     
         26 . The method of  claim 14 , wherein the liposome has a lipid to active platinum compound ratio of about 100:1 to about 400:1 by weight. 
     
     
         27 . The method of  claim 26 , wherein the lipid to active platinum compound ratio is about 200:1 to 400:1 by weight. 
     
     
         28 . The method of  claim 1 , wherein the active platinum compound is selected from the group consisting of cisplatin, carboplatin (diammine(1,1-cyclobutanedicarboxylato)-platinum(II)), tetraplatin (ormaplatin) (tetrachloro(1,2-cyclohexanediamine-N,N′)-platinum(IV)), thioplatin (bis(O-ethyldithiocarbonato)platinum(II)), satraplatin, nedaplatin, oxaliplatin, heptaplatin, iproplatin, transplatin, lobaplatin, cis-aminedichloro(2-methylpyridine) platinum, JM118 (cis-amminedichloro (cyclohexylamine)platinum(II)), JM149 (cis-amminedichloro(cyclohexylamine)-trans-dihydroxoplatinum(IV)), JM216 (bis-acetato-cis-amminedichloro(cyclohexylamine) platinum(IV)), JM335 (trans-amminedichloro (cyclohexylamine)dihydroxoplatinum(IV)), (trans, trans, trans)bis-mu-(hexane-1,6-diamine)-mu-[diamine-platinum(II)]bis[diamine(chloro) platinum(II)]tetrachloride, and mixture thereof. 
     
     
         29 . The method of  claim 30 , wherein the active platinum compound is cisplatin. 
     
     
         30 . The method of  claim 1 , wherein the lipid-complexed active platinum compound comprises a phosphatidyl choline. 
     
     
         31 . The method of  claim 30 , wherein the phosphatidyl choline is DPPC. 
     
     
         32 . The method of  claim 31 , wherein the lipid-complexed active platinum compound further comprises a sterol. 
     
     
         33 . The method of  claim 30 , wherein the sterol is cholesterol. 
     
     
         34 . The method of  claim 30 , wherein the lipid-complexed active platinum compound does not comprise a negatively charged phospholipid. 
     
     
         35 . The method of  claim 30 , wherein the lipid complexed active platinum compound comprises DPPC and cholesterol in a ratio of about 1:1 to about 5:1 by weight. 
     
     
         36 . The method of  claim 35 , wherein the lipid complexed active platinum compound comprises DPPC and cholesterol in a ratio of about 2:1 to about 4:1 by weight. 
     
     
         37 . The method of  claim 36 , the lipid complexed active platinum compound comprises DPPC and cholesterol in a ratio of about 2.25:1 by weight. 
     
     
         38 . The method of  claim 1 , wherein the cancer is selected from the following: melanoma, testis (germ cell), 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, or squamous cell carcinomas of the head and neck. 
     
     
         39 . The method of  claim 1 , wherein the cancer is ovarian cancer. 
     
     
         40 . The method of  claim 1 , wherein the cancer is colon cancer. 
     
     
         41 . The method of  claim 1 , wherein the patient is a human. 
     
     
         42 . The method of  claim 1 , wherein the composition is administered to the patient at least once every three weeks. 
     
     
         43 . The method of  claim 1 , wherein the amount of platinum compound in the composition is 60 mg/m 2  or greater, 100 mg/m 2  or greater, 140 mg/m 2  or greater, or 180 mg/m 2  or greater. 
     
     
         44 . The method of  claim 1 , wherein the amount of platinum compound in the composition is 100 mg/m 2  or greater, and the composition is administered to the patient at least once every three weeks.