System and method for diagnosis and treatment
This invention relates to a low cost rapid response diagnostic system to determine cortisol levels in patients selected as potential candidates for GCR (glucocorticoid receptor) antagonist therapy utilizing a GCR antagonist, such as ORG 34517. The rapid, sensitive, and inexpensive test can be used to determine patients who have non-normal cortisol production or disordered circadian rhythms as a method for selecting subjects for GCR antagonist therapy for whom it is likely to have beneficial and/or therapeutic effects, and can also be used to monitor changes in cortisol levels in response to treatment.
1. A pharmaceutical composition for treating neoplasia in a patient which is characterized by expression of a glucocorticoid receptor, comprising:
a) therapeutically effective amounts of at least one neoplasia-treating agent selected from, taxanes wherein the taxane is paclitaxel and docetaxel, and combinations thereof;
b) a GCR (glucocorticoid receptor) antagonist selected from the group consisting of ORG 34517, 11-(substituted phenyl)-estra-4,9-diene derivatives, and 11-(substituted phenyl)-estra-4,9-diene derivatives of formula I
wherein A is a residue of a 5- or 6-membered ring containing 2 heteroatoms which are not connected to each other and independently selected from O and S, the ring being optionally substituted with one or more halogen atoms, or A is a residue of a 5- or 6-membered ring wherein no double C—C bonds are present, containing 1 heteroatom selected from O and S, which heteroatom is connected to the phenyl group at the position indicated with an asterisk, the ring being optionally substituted with one or more halogen atoms; R1 is H or 1-oxo(1-4C)alkyl; R2 is H, (1-8C)alkyl, halogen or CF3; X is selected from (H,OH), O, and NOH; and the interrupted line represents an optional bond; and
c) optionally, at least one pharmaceutically acceptable carrier;
wherein the neoplasia is selected from the group consisting of hepatocellular carcinoma, breast cancer, ovarian cancer, and combinations thereof.
2. The pharmaceutical composition of claim 1 , wherein the neoplasia is chemo-resistant ER−/GR+breast cancer.
3. The pharmaceutical composition of claim 1 , wherein the neoplasia expresses multidrug resistance genes when GR is activated through binding by endogenous cortisol.