Abstract
In a previous 15-day, Phase II study of patients with de novo or persistent/recurrent Cushing’s disease (core study), treatment with pasireotide 600 μg sc bid reduced urinary free cortisol (UFC) levels in 76 % of patients and normalized UFC in 17 %. The objective of this study was to evaluate the efficacy and safety of extended treatment with pasireotide. This was a planned, open-ended, single-arm, multicenter extension study (primary endpoint: 6 months). Patients aged ≥18 years with Cushing’s disease who completed the core study could enter the extension if they achieved UFC normalization at core study end and/or obtained significant clinical benefit. Of the 38 patients who completed the core study, 19 entered the extension and 18 were included in the efficacy analyses (three responders, 11 reducers, four non-reducers in the core study). At data cut-off, median treatment duration in the extension was 9.7 months (range: 2 months to 4.8 years). At extension month 6, 56 % of the 18 patients had lower UFC than at core baseline and 22 % had normalized UFC. Of the four patients who remained on study drug at month 24, one had normalized UFC. Reductions in serum cortisol, plasma adrenocorticotropic hormone, body weight and diastolic blood pressure were observed. The most common adverse events were mild-to-moderate gastrointestinal disorders and hyperglycemia. Pasireotide offers a tumor-directed medical therapy that may be effective for the extended treatment of some patients with Cushing’s disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s11102-013-0503-3) contains supplementary material, which is available to authorized users.
Highlights
Cushing’s disease is the clinical consequence of chronic hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma [1]
After 6 months of therapy, 10 of 18 patients (56 %) achieved reduced urinary free cortisol (UFC) levels compared with core baseline, and four patients (22 %) had normalized UFC levels
Mean serum cortisol and plasma ACTH levels decreased over this period, irrespective of whether UFC control was achieved
Summary
Cushing’s disease is the clinical consequence of chronic hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma [1]. Patients with Cushing’s disease have 4.8-fold higher mortality than the general population [2] and a high level of cardiovascular, metabolic and osteoporotic comorbidities [2,3,4]. First-line treatment for patients with Cushing’s disease is transsphenoidal surgery, with remission rates of 65–90 % in patients with a microadenoma, if performed by an expert pituitary surgeon [1]. Second-line options include repeat surgery, radiotherapy, medical therapy and bilateral adrenalectomy [1]. Lower success rates are seen after repeat surgery than after the initial surgery, and hypopituitarism is more common [1]. Hypopituitarism is common after radiotherapy [5], whereas bilateral adrenalectomy results in permanent hypoadrenalism [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
