Method of treating prostatic diseases using active vitamin D analogues
AssigneeBone Care International, Inc.
InventorsCharles W. Bishop, Joyce C. Knutson, Richard B. Mazess
Life of this patent
Estimating the term…
Abstract
The invention provides therapeutic methods for inhibiting, ameliorating or alleviating the hyperproliferative cellular activity of diseases of the prostate, e.g., prostatic cancer and prostatic hyperplasia, which includes administering to a patient in need thereof an active vitamin D analogue. Cell differentiation is promoted, induced or enhanced without causing to the patient dose-limiting hypercalcemia and hypercalciuria.
Claims18
A method of inhibiting the hyperproliferative activity of human prostatic neoplastic or hyperplastic cells, comprising treating the cells with an effective amount of a 1α-hydroxyvitamin D compound having a hydrocarbon moiety substituted at C-24.
A method for the treatment of prostatic diseases characterized by abnormal cell differentiation or cell proliferation, comprising administering to a male human or animal in need of such treatment an effective proliferation-inhibiting amount of a compound of formula (I)
- 3
- wherein B and C each are hydrogen or a carbon-carbon bond, thus forming a double bond between C-22 and C-23;
- R1 and R2 are identical or different and are hydrogen, hydroxyl, lower alkyl, lower fluoroalkyl, O-lower alkyl, lower alkenyl, lower fluoroalkenyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl, lower cycloalkyl with the proviso that R1 and R2 cannot both be an alkenyl group, or taken together with the carbon to which they are bonded, form a C3-C8 cyclocarbon ring;
- R3 is lower alkyl, lower alkenyl, lower fluoroalkyl, lower fluoroalkenyl, O-lower alkyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl or lower cycloalkyl;
- X1 is hydrogen or hydroxyl, or, taken with R3, constitutes a bond when R3 is an alkenyl group, and X2 is hydrogen or hydroxyl, or, taken with R1 or R2, constitutes a double bond.
A method of treating human prostate cancer, comprising administering to a male subject, who has prostate cancer, an effective amount of a first anticancer agent which is an active vitamin D compound to decrease or stabilize the cellular abnormal proliferative activity of the cancer, said compound or its in vivo metabolite having a VDR binding affinity substantially equivalent to the binding affinity of 1α,25-dihydroxyvitamin D3 and a hypercalcemia risk substantially lower than that of 1α,25-dihydroxyvitamin D3.
A pharmaceutical composition, comprising
- (a) a first anticancer agent which is an active vitamin D compound, and
- (b) an agent selected from the group consisting of (i) a second anticancer agent, (ii) a bone agent, (iii) an androgen control agent and (iv) a 5α-reductase inhibitor and combinations thereof.
A method of treating a human to alleviate the hyperproliferative cellular activity of prostatic cancer or hyperplasia, comprising administering to a human in need thereof a therapeutically effective amount of an active vitamin D compound having a hydrocarbon moiety substituted at C-24.
Dependencies are inferred from the claim text.