Endoxifen For Local Transdermal Therapy To The Breast
Disclosed are methods and topical formulations for treating and/or preventing cell proliferative diseases and disorders including breast cancer and ductal carcinoma is situ (DCIS) using local transdermal therapy (LTT). The disclosed methods typically include administering topically to the breast or breasts of the patient a topical formulation comprising an effective dose of the tamoxifen metabolite, N-desmethyl-4-hydroxytamoxifen (i.e., endoxifen or ENX) for treating breast cancer. The topical formulation may be described as a transdermal formulation and the topical formulation may comprise, consist essentially of, or consist of endoxifen as an active ingredient.
1 . A method for treating and/or preventing breast cancer and ductal cancer in situ (DCIS) in a patient in need thereof, the method comprising administering topically to the breast or breasts of the patient a topical formulation comprising an effective dose of endoxifen for treating breast cancer.
2 . The method of claim 1 , wherein the topical formulation is a transdermal formulation comprising one or more chemical permeation enhancers (CPEs).
3 . The method of claim 1 , wherein the topical formulation comprises a fatty acid at a concentration of about 0.1%-5% (w/w), the fatty acid having a melting temperature of less than about 20° C.
4 . The method of claim 3 , wherein the fatty acid is oleic acid.
5 . The method of claim 1 , wherein the topical formulation comprises alcohol at a concentration of about 40%-80% (w/w).
6 . The method of claim 1 , wherein the topical formulation is a gel comprising a gelling polymer at a concentration of about 0.1%-0.5% (w/w).
7 . The method of claim 1 , wherein the endoxifen is present in the topical formulation at a concentration of about 0.1 mg/ml-10 mg/ml.
8 . The method of claim 1 , wherein the endoxifen is administered at a dose per bodyweight of the patient of about 1.0-20 mg/kg/day.
9 . The method of claim 1 , wherein the dose of endoxifen delivered to the breast of the patient is at least about 1.0-20 ng/g and the dose delivered to the plasma of the patient is no more than about 5 ng/ml.
10 . The method of claim 1 , wherein the ratio (R) of the dose of endoxifen delivered to the breast of the patient (D Breast in ng/g) to the dose delivered to the plasma of the patient (D Plasma in ng/ml) is greater than about 5.
11 . A topical formulation for treating and/or preventing breast cancer and ductal cancer in situ (DCIS) in a patient in need thereof, the topical formulation comprising an effective dose of endoxifen for treating breast cancer.
12 . The topical formulation of claim 11 , wherein the topical formulation is a transdermal formulation comprising one or more chemical permeation enhancers (CPEs).
13 . The topical formulation of claim 11 , wherein the topical formulation comprises a fatty acid at a concentration of about 0.1%-5% (w/w), the fatty acid having a melting temperature of less than about 20° C.
14 . The topical formulation of claim 13 , wherein the fatty acid is oleic acid.
15 . The topical formulation of claim 11 , wherein the topical formulation comprises alcohol at a concentration of about 40%-80% (w/w).
16 . The topical formulation of claim 11 , wherein the topical formulation is a gel comprising a gelling polymer at a concentration of about 0.1%-0.5% (w/w).
17 . The topical formulation of claim 11 , wherein the endoxifen is present in the topical formulation at a concentration of about 0.1 mg/ml-10 mg/ml.
18 . The topical formulation of claim 11 , wherein the topical formulation is formulated to deliver a dose of endoxifen per bodyweight of the patient of about 1.0-20 mg/kg/day.
19 . The topical formulation of claim 11 , wherein the dose of endoxifen delivered to the breast of the patient is at least about 1.0-20 ng/g and the dose delivered to the plasma of the patient is no more than about 5 ng/ml.
20 . The topical formulation of claim 11 , wherein the topical formulation is formulated to deliver a dose of endoxifen to the breast of the patient (D Breast ) and a dose of endoxifen to the plasma of the patient (D Plasma ) and the ratio (R) of the dose of endoxifen delivered to the breast of the patient (D Breast in ng/g) to the dose delivered to the plasma of the patient (D Plasma in ng/ml) is greater than about 5.