THERAPEUTIC COMBINATIONS OF ORALLY ADMINISTERED PACLITAXEL AND A P-gp INHIBITOR FOR THE TREATMENT OF ANGIOSARCOMA
The application pertains to pharmaceutical combinations of orally administered paclitaxel and a P-gp inhibitor. The pharmaceutical combinations are suitable for the treatment of an angiosarcoma in a subject and for reducing or preventing toxicity, hypersensitivity-type infusion reactions, and other negative outcomes resulting from or associated with intravenously administered paclitaxel (e.g., Taxol® or paclitaxel formulated with Cremophor®) therapy in a subject suffering from an angiosarcoma.
1 . A method for treating an angiosarcoma in a subject in need thereof, comprising:
a. oral administration of paclitaxel at an amount of about 205 mg/m 2 to the subject once a day and for 3 times a week; and
b. oral administration of Compound A:
to the subject once a day and for 1-3 times a week, and
wherein Compound A is administered prior to the paclitaxel.
2 . The method of claim 1 , comprising oral administration of paclitaxel on consecutive days.
3 . The method of claim 1 , comprising oral administration of Compound A at an amount of about 15 mg.
4 . The method of claim 1 , comprising oral administration of Compound A for 3 times a week.
5 . The method of claim 1 , comprising oral administration of Compound A on consecutive days.
6 . The method of claim 1 , comprising oral administration of Compound A at an amount of about 15 mg and for 3 times a week.
7 . The method of claim 6 , comprising oral administration of paclitaxel on consecutive days.
8 . The method of claim 6 , comprising oral administration of Compound A on consecutive days.
9 . The method of claim 6 , wherein Compound A is administered about an hour prior to the paclitaxel.
10 . The method of claim 1 , wherein the angiosarcoma is cutaneous angiosarcoma.
11 . A method for treating an angiosarcoma in a subject in need thereof, comprising:
a. oral administration of paclitaxel at an amount of about 205 mg/m 2 to the subject once a day and for 3 times a week for a first duration, and at a second amount less than 205 mg/m 2 to the subject once a day and for 3 times a week for a second duration;
b. oral administration of Compound A:
to the subject once a day and for 1-3 times a week, and
wherein Compound A is administered prior to the paclitaxel.
12 . The method of claim 11 , wherein the second amount is about 165 mg/m 2 .
13 . The method of claim 11 , wherein the second amount is about 130 mg/m 2 .
14 . The method of claim 11 , comprising oral administration of Compound A at an amount of about 15 mg and for 3 times a week.
15 . The method of claim 11 , wherein the angiosarcoma is cutaneous angiosarcoma.
16 . A method for treating an angiosarcoma in a subject in need thereof, comprising:
a. oral administration of paclitaxel at an amount of about 205 mg/m 2 to the subject once a day and for 3 times a week for a first duration, at a second amount less than 205 mg/m 2 to the subject once a day and for 3 times a week for a second duration, and at a third amount less than the second amount to the subject once a day and for 3 times a week;
b. oral administration of Compound A:
to the subject once a day and for 1-3 times a week, and
wherein Compound A is administered prior to the paclitaxel.
17 . The method of claim 16 , wherein the second amount is about 165 mg/m 2 .
18 . The method of claim 16 , wherein the third amount is about 130 mg/m 2 .
19 . The method of claim 16 , comprising oral administration of Compound A at an amount of about 15 mg and for 3 times a week.
20 . The method of claim 16 , wherein the angiosarcoma is cutaneous angiosarcoma.