Liposomal Camptothecins and Uses Thereof
This invention relates to improved liposomal camptothecin compositions and methods of manufacturing and using such compositions for treating neoplasia and for inhibiting angiogenesis.
1 . A liposomal topotecan unit dosage form, said unit dosage form comprising: a lipid; and a topotecan dosage of from about 0.01 mg/M 2 /dose to about 7.5 mg/M 2 /dose, wherein said liposomal topotecan unit dosage form has a drug:lipid ratio (by weight) of about 0.05 to about 0.2.
2 . The liposomal topotecan unit dosage form of claim 1 , wherein said drug:lipid ratio (by weight) is about 0.05 to about 0.15.
3 . The liposomal topotecan unit dosage form of claim 1 , wherein said lipid comprises a mixture of sphingomyelin and cholesterol.
4 . The liposomal topotecan unit dosage form of claim 1 , wherein said lipid comprises sphingomyelin and cholesterol in a ratio by weight of about 30:70 to about 60:40.
5 . The liposomal topotecan unit dosage form of claim 1 , comprising from about 1 mg/M 2 /dose to about 4 mg/M 2 /dose of topotecan.
6 . A liposomal topotecan formulation, wherein said liposomal topotecan formulation retains greater than 50% active lactone species after 12 hours in blood circulation.
7 . The liposomal topotecan formulation of claim 6 , wherein said liposomal topotecan formulation retains greater than 80% active lactone species after 12 hours in blood circulation.
8 . A liposomal topotecan formulation comprising topotecan, sphingomyelin, cholesterol and a divalent cation ionophore.
9 . The liposomal topotecan formulation of claim 8 , wherein said divalent ionophore is present in trace amounts.
10 . The liposomal topotecan formulation of claim 8 , comprising a drug:lipid ratio (by weight) of about 0.05 to about 0.2.
11 . The liposomal topotecan formulation of claim 10 , wherein said drug:lipid ratio (by weight) is about 0.05 to about 0.15
12 . The liposomal topotecan formulation of claim 11 , comprising trace amounts or greater of a divalent ionophore.
13 . A method of treating a solid tumor in a human afflicted therewith, said method comprising administering to said human an effective amount of a topotecan dosage of claim 1 in a pharmaceutically acceptable carrier.
14 . The method of claim 13 , wherein said solid tumor is selected from the group consisting of solid tumors of the lung, mammary, colon and prostate.
15 . The method of claim 13 , further comprising co-administration of a treatment for neutropenia or platelet deficiency.
16 . A method of treating solid tumors in a mammal, said method comprising: administering to said mammal having a solid tumor of the lung, mammary and/or colon a liposomal topotecan formulation having a drug:lipid ratio (by weight) of about 0.05 to about 0.2.
17 . A method of treating solid tumors in a mammal, said method comprising: administering to said mammal having a solid tumor of the lung, mammary and/or colon a liposomal topotecan formulation comprising from about 0.01 mg/M 2 /dose to about 7.5 mg/M 2 /dose of topotecan for an interval regime, wherein said interval regime is once a day for at least two consecutive days.
18 . The method of treating solid tumors of claim 17 , wherein said interval regime is at least once a week.
19 . The method of treating solid tumors of claim 17 , wherein said interval regime is at least once every two weeks.
20 . The method of treating solid tumors of claim 17 , wherein said interval regime is at least once every three weeks.
21 . The method of treating solid tumors of claim 17 , wherein said liposomal topotecan formulation has a drug:lipid ratio (by weight) of about 0.05 to about 0.2.
22 . A method of treating solid tumors in a mammal comprising administering to an animal having a solid tumor of the lung, mammary and/or colon a liposomal topotecan formulation comprising from about 0.01 to about 7.5 mg/M 2 /dose of topotecan every three days.
23 . A liposomal camptothecin unit dosage form, said unit dosage form comprising a lipid, a camptothecin dosage of from about 0.015 mg/M 2 /dose to about 1 mg/M 2 /dose and having a drug:lipid ratio (by weight) of about 0.05 to about 0.2.
24 . The use of topotecan in the manufacture of a medicament comprising a liposome having a sphingomyelin to cholesterol ratio (by weight) of from about 30:70 to about 60:40 for use in treating solid tumors in a mammal.
25 . The use of claim 24 , for treating solid tumors of the lung, mammary and colon.