Pasireotide in Cushing's Disease

ArticleinNew England Journal of Medicine 366(22):2134; author reply 2134-5 · May 2012with1 Reads
DOI: 10.1056/NEJMc1204078#SA1 · Source: PubMed
    • "Despite variability in serum cortisol levels, there was an overall reduction in serum cortisol and plasma ACTH relative to the core baseline that was maintained throughout the extension phase [14]. A recently published study case report illustrated long-term UFC control without escape or serious adverse event during more than 7 years of treatment with subcutaneous pasireotide [17] . A randomized, doubleblind , multicenter, phase III study to evaluate the efficacy and safety of pasireotide long acting release (LAR) in patients with Cushing's disease is now underway [18]. "
    [Show abstract] [Hide abstract] ABSTRACT: Cushing's disease is a condition of hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. While rare, it is associated with significant morbidity and mortality, which suggests that early and aggressive intervention is required. The primary, definitive therapy for patients with Cushing's disease in the majority of patients is pituitary surgery, generally performed via a transsphenoidal approach. However, many patients will not achieve remission or they will have recurrences. The consequences of persistent hypercortisolism are severe and, as such, early identification of those patients at risk of treatment failure is exigent. Medical management of Cushing's disease patients plays an important role in achieving long-term remission after failed transsphenoidal surgery, while awaiting effects of radiation or before surgery to decrease the hypercortisolemia and potentially reducing perioperative complications and improving outcome. Medical therapies include centrally acting agents, adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers. Furthermore, several new agents are in clinical trials. To normalize the devastating disease effects of hypercortisolemia, it is paramount that successful patient disease management includes individualized, multidisciplinary care, with close collaboration between endocrinologists, neurosurgeons, radiation oncologists, and general surgeons. This commentary will focus on recent advances in the medical treatment of Cushing's, with a focus on newly approved ACTH modulators and glucocorticoid receptor blockers.
    Full-text · Article · Mar 2014
    • "The use of some inhibitors of ACTH production has been described, but they are ineffective in treating Cushing’s disease [22]. However, it has recently been reported that the use of pasireotide, a somatostatin analogue, has shown success in treating this disease [23], [24]. At the same way, it is essential to prospect for new drugs that could constitute an efficient pharmacological approach to treat Cushing’s disease. "
    [Show abstract] [Hide abstract] ABSTRACT: Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1) in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27(kip1) in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1); and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.
    Full-text · Article · May 2013
  • [Show abstract] [Hide abstract] ABSTRACT: In Czech Republic, new somatostatin analog - pasireotide (SOM230, Signifor* Novartis Pharma) will be available to the therapeutic use at the end of this year. The main indication is the central hypercortisolism caused by ACTH secreting pituitary adenomas. When used in monotherapy, in 25% of these patients, the normalization of urinary free Cortisol was achieved after a year's treatment using 2 x 900 ug in s.c. injections daily, meanwhile in combination with cabergoline and ketoconazole this effect increased to 88%. Adenoma size at this dose and length of treatment reduced in average of 43.8%. Pasireotide is tested in the treatment of acromegaly and neuroendocrine tumors as well. Here it can profit of the effect in patients resistant to octreotide. It is caused by the strong binding of pasireotide to the somatostatin receptor SSTR5, where other somatostatin analogues bind 40-100 times less. The main adverse event of pasireotide is the hyperglycemic effect. Other adverse events are consistent with side effects of other somatostatin analogues. The treatment will become more comfortable with newly developed long-acting pasireotide (pasireotdie LAR) injected once in 28 days.
    Article · Jan 2012
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