Vitamin D and its analogs in the treatment of tumors and other hyperproliferative disorders
First Claim
1. A method for the treatment of a hyperproliferative disease in a subject, wherein the hyperproliferative disease responds to treatment with a Vitamin D drug, comprising repeatedly administering to the subject a therapeutically effective pulse dose of the Vitamin D drug, no more frequently than once in three days, in a pulse dose of about 0.12 mcg/kg per day to about 2.8 mcg/kg per day, each pulsed dose being in a sufficient amount to have an antiproliferative effect, without inducing severe symptomatic hypercalcemia in the subject, wherein the Vitamin D drug is 25-hydroxyvit D3 or 1,25-dihydroxycholecalciferol.
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Abstract
Treatment of hyperporliferative disorders (including tumors and psoriasis) by pulse administration of a drug (such as Vitamin D or an analog) that increases blood or tissue levels of Vitamin D. The drug is administered at a sufficient dose to have an anti-proliferative effect, but the pulsed administration of the drug avoids the development of severe symptomatic or life-threatening hypercalcemia. In particular embodiments, avoidance of hypercalcemia (as measured by serum levels of calcium above normal range) is avoided altogether. In a particular example, the drug is calcitriol administered at an oral dose of about 0.5 mcg/kg once a week.
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Citations
54 Claims
- 1. A method for the treatment of a hyperproliferative disease in a subject, wherein the hyperproliferative disease responds to treatment with a Vitamin D drug, comprising repeatedly administering to the subject a therapeutically effective pulse dose of the Vitamin D drug, no more frequently than once in three days, in a pulse dose of about 0.12 mcg/kg per day to about 2.8 mcg/kg per day, each pulsed dose being in a sufficient amount to have an antiproliferative effect, without inducing severe symptomatic hypercalcemia in the subject, wherein the Vitamin D drug is 25-hydroxyvit D3 or 1,25-dihydroxycholecalciferol.
- 9. A method of treating a tumor in a subject, wherein the tumor expresses a Vitamin D receptor and is responsive to treatment with a Vitamin D drug, the method comprising repeatedly administering orally to the subject, once in a three to ten day period, a dose of calcitriol, wherein each dose of calcitriol is a therapeutically effective dose, of about 0.12 mcg/kg to about 2.8 mcg/kg, sufficient to have an antiproliferative effect, without inducing severe symptomatic hypercalcemia in the subject.
- 12. A method of treating in a subject a tumor that expresses a Vitamin D receptor, the method comprising repeatedly administering a dose of a Vitamin D drug to raise a blood level of the Vitamin D drug to a sufficiently supraphysiologic level for a sufficient period of time to inhibit growth of the tumor, wherein each dose of the Vitamin D drug is sufficient to inhibit tumor growth without inducing hypercalcemia in the subject, wherein the Vitamnin D drug is 25-hydroxyvitamin D3 or 1,25-dihydroxycholecalciferol and the dose is administered no more than once in 3-10 days, and wherein the Vitamin D drug is admistered in a dose of about 0.12 mcg/kg per day to about 2.8 mcg/kg per day.
- 15. A method of administering a Vitamin D drug to a subject in need thereof, the method comprising repeatedly administering therapeutically effective pulse doses of the Vitamin D drug wherein each dose is sufficient to achieve intermittent antiproliferative therapeutic levels of the Vitamin D drug, and wherein the pulse doses are administered separated by 3-10 days to avoid symptomatic hypercalcemia, and wherein each dose is about 0.12 mcg/kg per day to about 2.8 mcg/kg per day and the Vitamin D drug is 25-hydroxyvitamin D3 or 1,25-dihydroxycholecalciferol.
- 41. A method of administering a Vitamin D drug to a subject at an anti-hyperproliferative dose substantially without symptomatic significant hypercalcemia, wherein the method comprises repeatedly administering therapeutically effective pulsed doses of the Vitamin D drug, wherein each dose of the Vitamin D drug is a dose that is sufficient to have an antiproliferative effect, the dose is repetitively administered separated by 3-10 days, and the Vitamin D drug is calcitriol, and wherein the dose is about 0.12 mcg/kg per day to about 2.8 mcg/kg per day.
Specification