PREVENTING OR MITIGATING CHEMOTHERAPY INDUCED ALOPECIA USING VITAMIN D
The invention provides methods and pharmaceutical compositions for preventing or mitigating chemotherapy-induced alopecia (CIA). The pharmaceutical compositions of the invention comprise an effective amount of a vitamin D compound in a topical formulation. The invention has broad applications in chemotherapies that induce alopecia, for example taxane based chemotherapy for cervical cancer, endometrial cancer, ovarian cancer, fallopian tube cancer, primary peritoneal carcinoma, soft tissue sarcoma, or bone sarcoma. The pharmaceutical compositions of the invention can be advantageously administered before and/or concurrent with the chemotherapy.
1 . A method of preventing or mitigating chemotherapy-induced alopecia in a human subject comprising the steps of:
(1) selecting a human subject having a cancer and who is scheduled to receive, or is receiving, a chemotherapy; and
(2) topically administering a pharmaceutical composition comprising a vitamin D compound in a total daily dose of 105 μg to 180 μg of the vitamin D compound to the scalp of the subject,
wherein step (2) is performed prior to and/or concurrently with the chemotherapy, thereby preventing or mitigating chemotherapy-induced alopecia in the subject.
2 . The method of claim 1 , wherein the pharmaceutical composition is administered in a total daily dose of 120 μg to 160 μg of the vitamin D compound.
3 - 4 . (canceled)
5 . The method of claim 1 , wherein the pharmaceutical composition comprises the vitamin D compound at a concentration of 50 μg/ml to 100 μg/ml.
6 - 8 . (canceled)
9 . The method of claim 1 , wherein the pharmaceutical composition is administered in an about 1.0 mL dose.
10 . The method of claim 9 , wherein about 0.25 mL is administered to each of the four quadrants of the scalp.
11 . The method of claim 1 , wherein the pharmaceutical composition is administered twice daily.
12 . (canceled)
13 . The method of claim 1 , wherein the pharmaceutical composition is administered using a metered spray unit.
14 . The method of claim 13 , wherein the metered spray unit dispenses a volume of about 0.25 mL for one or multiple of four times.
15 . The method of claim 1 , wherein step (2) is performed prior to the commencement of the chemotherapy.
16 . The method of claim 1 , wherein step (2) is performed for a sufficient time prior to the commencement of the chemotherapy such that the catagen stage of hair follicles is induced in the treated area of the subject.
17 . The method of claim 16 , wherein step (2) is performed at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 days prior to the commencement of the chemotherapy.
18 . (canceled)
19 . The method of claim 1 , wherein the subject has a solid tumor.
20 - 27 . (canceled)
28 . The method of claim 1 , wherein the pharmaceutical composition is formulated such that the vitamin D compound is delivered to epidermis while substantially avoiding dermal delivery.
29 . The method of claim 1 , wherein the pharmaceutical composition is anhydrous.
30 . The method of claim 1 , wherein the pharmaceutical composition comprises a vehicle of about 40% (w/w) propylene glycol and about 60% (w/w) anhydrous ethanol.
31 . The method of claim 1 , wherein the pharmaceutical composition comprises a vehicle of about 30% (w/w) propylene glycol, about 10% (w/w) ethoxydiglycol or transcutol, and about 60% (w/w) anhydrous ethanol.
32 . (canceled)
33 . The method of claim 1 , wherein the vitamin D compound is calcitriol.
34 - 37 . (canceled)
38 . The method of claim 1 , wherein the vitamin D compound is
calcitriol, wherein the pharmaceutical composition comprises calcitriol at a concentration of about 60 μg/ml and is administered in an about 1.0 mL dose twice daily using a metered spray unit, wherein about 0.25 mL is administered to each of the four quadrants of the scalp; and
wherein step (2) is performed prior to and/or concurrently with the chemotherapy, thereby preventing or mitigating chemotherapy-induced alopecia in the subject.
39 . (canceled)
40 . The method of claim 1 , wherein the vitamin D compound is
calcitriol, wherein the pharmaceutical composition comprises calcitriol at a concentration of about 80 μg/ml and is administered in an about 1.0 mL dose twice daily using a metered spray unit, wherein about 0.25 mL is administered to each of the four quadrants of the scalp; and
wherein step (2) is performed prior to and/or concurrently with the chemotherapy, thereby preventing or mitigating chemotherapy-induced alopecia in the subject.
41 - 43 . (canceled)
44 . A metered spray unit comprising a pharmaceutical composition which comprises a vitamin D compound at a concentration of about 50 μg/mL to about 100 μg/mL.
45 - 52 . (canceled)