Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2014
Pasireotide and mifepristone: new options in the medical management of Cushing's disease.
СтатьяПоддержка исследования: вне правительства СШАОбзорНазвание и аннотация: Перевод в очереди
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Cohan Pejman
Аннотация
OBJECTIVE: To review and evaluate medical therapies for Cushing's disease (CD), with an emphasis on recent clinical trial experience with pasireotide and mifepristone, and to discuss the therapeutic potential and appropriate selection of these compounds in this patient population.
METHODS: Recently published Phase III trial data for each compound are reviewed and assessed, and relative benefits and risks are examined and compared where possible.
RESULTS: Mifepristone and pasireotide are both potentially beneficial for CD patients but have greatly dissimilar mechanisms of action and adverse event (AE) profiles. Pasireotide acts at the level of the pituitary adenoma, reducing cortisol levels through inhibition of adrenocorticotropic hormone (ACTH) release. However, pasireotide reduces insulin secretion and incretin hormone response and is associated with significant risk for new or worsening hyperglycemia. Mifepristone ameliorates the signs and symptoms of hypercortisolemia via glucocorticoid receptor (GR2) blockade, but this approach raises serum cortisol levels and increases risk for adrenal insufficiency (AI), hypokalemia, and endometrial thickening. While response to pasireotide can be monitored via measurements of serum, urine, or late-night salivary cortisol, evaluation of response to mifepristone is solely based on changes in clinical parameters (e.g., hyperglycemia, hypertension, body weight/composition).
CONCLUSION: Management of persistent CD is challenging, and the decision to initiate medical treatment hinges on many factors. Pasireotide may be a more attractive option for most patients due to its action at the underlying tumor and the ability to monitor biochemical responses. However, mifepristone may be more appropriate when it is necessary to avoid or minimize risk for hyperglycemia-related complications.
METHODS: Recently published Phase III trial data for each compound are reviewed and assessed, and relative benefits and risks are examined and compared where possible.
RESULTS: Mifepristone and pasireotide are both potentially beneficial for CD patients but have greatly dissimilar mechanisms of action and adverse event (AE) profiles. Pasireotide acts at the level of the pituitary adenoma, reducing cortisol levels through inhibition of adrenocorticotropic hormone (ACTH) release. However, pasireotide reduces insulin secretion and incretin hormone response and is associated with significant risk for new or worsening hyperglycemia. Mifepristone ameliorates the signs and symptoms of hypercortisolemia via glucocorticoid receptor (GR2) blockade, but this approach raises serum cortisol levels and increases risk for adrenal insufficiency (AI), hypokalemia, and endometrial thickening. While response to pasireotide can be monitored via measurements of serum, urine, or late-night salivary cortisol, evaluation of response to mifepristone is solely based on changes in clinical parameters (e.g., hyperglycemia, hypertension, body weight/composition).
CONCLUSION: Management of persistent CD is challenging, and the decision to initiate medical treatment hinges on many factors. Pasireotide may be a more attractive option for most patients due to its action at the underlying tumor and the ability to monitor biochemical responses. However, mifepristone may be more appropriate when it is necessary to avoid or minimize risk for hyperglycemia-related complications.