Use of glucocorticoid receptor modulators in the treatment of catecholamine-secreting tumors

A glucocorticoid, receptor modulator technology, applied in the therapy and composition of patients with Cushing's syndrome, the treatment of Cushing's syndrome patients with neuroendocrine tumors, the field of Cushing's syndrome in patients, to achieve improved methods and treatment effects

Pending Publication Date: 2019-11-19
CORCEPT THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Finally, patients with metastatic disease without large lesions may be eligible for MIBG

Method used

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  • Use of glucocorticoid receptor modulators in the treatment of catecholamine-secreting tumors
  • Use of glucocorticoid receptor modulators in the treatment of catecholamine-secreting tumors
  • Use of glucocorticoid receptor modulators in the treatment of catecholamine-secreting tumors

Examples

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Effect test

Embodiment 1

[0194] A phase 2 study of somatostatin analogues in a 53-year-old female patient with metastatic pheochromocytoma associated with ectopic ACTH secretion, response to CVD (cyclophosphamide, vincristine, and dacarbazine ) and sunitinib (tyrosine kinase inhibitor) conventional chemotherapy unresponsive. After 3 months of treatment, despite high doses of atenolol (beta-blocker) and phenoxybenzamine (alpha-blocker), her metanephrine levels were still significantly elevated High and continue to experience significant catecholamine overdose symptoms (palpitations, tremors, and panic attacks). At the same time, a diagnosis of Cushing's syndrome was made, and 300 mg of mifepristone was added to his treatment regimen, which was further increased to 600 mg per day after two weeks. After one week of taking mifepristone, a significant improvement in symptoms of cortisol excess and catecholamine excess was noted. Plasma adrenaline levels were reduced by 50% after 2 weeks of mifepristone t...

Embodiment 2

[0196] Patients with metastatic or unresectable catecholamine-secreting tumors were given an effective amount of mifepristone at a daily dose of 50 mg / kg / day, said patients did not require treatment with glucocorticoid receptor antagonists and were not receiving Treatment with exogenous glucocorticoid receptor agonists. Measurements showed that blood levels of catecholamines were lower after five weeks of treatment compared to initial levels.

Embodiment 3

[0198] Patients with metastatic or unresectable catecholamine-secreting tumors were given an effective amount of mifepristone at a daily dose of 20 mg / kg / day, said patients did not require treatment with glucocorticoid receptor antagonists and were not receiving Treatment with exogenous glucocorticoid receptor agonists. Measurements showed that blood levels of catecholamines were lower after five weeks of treatment compared to initial levels.

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Abstract

Novel methods of treating tumors, including neuroendocrine tumors (NET), such as a catecholamine-secreting tumor (CST), are disclosed. The methods include treating Cushing's syndrome in a Cushing's syndrome patient having a NET, such as a CST. Tumors may be treated with a glucocorticoid receptor (GR) modulator (GRM), such as a GR antagonist (GRA). The novel treatments may treat Cushing's syndrome,may reduce catecholamine production by the tumor, may reduce catecholamine excess, may ameliorate symptoms of catecholamine excess, and may improve the efficacy of alpha- or beta-adrenergic blockade,somatostatin or somatostatin analog treatment or imaging, or Peptide Receptor Radionuclide Therapy, in patients with a CST. The GRM may reduce the activation of a GR, and may bind to a GR with higheraffinity than it binds to a progesterone receptor (PR). In embodiments, the drug may only poorly bind to PR, or may not measurably bind to PR.

Description

Background technique [0001] Cushing's syndrome is characterized by high levels of cortisol. Cushing's syndrome is associated with hypercortisolemia, a condition of chronically excessive circulating cortisol. Cushing's syndrome can be divided into exogenous Cushing's syndrome and endogenous Cushing's syndrome. pine), endogenous Cushing's syndrome is caused by dysregulated abnormalities of the HPA axis. Patients with Cushing's syndrome typically have easy bruising; abdominal obesity with thin arms and legs; facial puffiness; acne; proximal muscle weakness; and / or reddish-purple streaks on the body. [0002] In endogenous Cushing, excess cortisol is usually due to cortisol-producing tumors, or tumors that elevate cortisol levels indirectly (for example, by causing an increase in adrenocorticotropic hormone (ACTH) or causing corticotropin release hormone (CRH) increases). Endogenous Cushing's syndrome includes: ACTH-independent Cushing's syndrome, characterized by excess corti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/57A61K51/08
CPCA61K31/575A61K45/06A61P35/00A61K31/435A61P3/00A61K31/517A61K31/4353A61P5/46
Inventor A·G·莫来提斯
Owner CORCEPT THERAPEUTICS INC
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