Treatment of pituitary dependent Cushing's disease with the multi-receptor ligand somatostatin analog pasireotide (SOM230): A multicenter, phase II trial.
Author(s) Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA, Bertherat J
Institution Department of Clinical Endocrinology (M.B.), University of Ancona, Italy; Seattle Pituitary Center (W.H.L.), Swedish Neurosciences Institute, Seattle, Washington, USA; Regional Centre for Endocrinology and Diabetes (B.A.), Royal Victoria Hospital, Belfast, UK; Oncology Clinical Development (J.E.G., C.H.D., K.H., Y.W.), Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Division of Endocrinology (S.P.), Medical Center, University of Essen, Germany; Medizinische Klinik Innenstadt Klinikum der Universität München (M.R.), München, Germany; University of Pennsylvania (P.S.), Philadelphia, USA; Service d'Endocrinologie (A.T.), CHU Bordeaux, Haut Lévêque, Pessac Cedex, France; Massachusetts General Hospital (B.M.K.B.), Boston, USA; Midwest Endocrinology Associates (J.F.), Milwaukee, Wisconsin, USA; Cedars-Sinai Pituitary Center (S.M.), Los Angeles, California, USA; Department of Medicine (P.U.F.), Division of Endocrinology, Columbia University, New York; Department of Endocrinology (A.B.G.), St Bartholomew's Hospital, London, UK; Department of Medicine (L.A.F.), Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA; Center for Rare Adrenal Diseases (J.B.), Department of Endocrinology, INSERM U567, Paris-Descartes University, Cochin Hospital, Paris, France.
Source J Clin Endocrinol Metab 2008 Oct 28.
Abstract Context: There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder.
Objective: To evaluate the short-term efficacy of the novel multi-receptor ligand somatostatin analog pasireotide in patients with de novo, persistent or recurrent Cushing's disease.
Design: Phase II, proof-of-concept, open-label, single-arm, 15-day multicenter.
Patients: Thirty-nine patients with either de novo Cushing's disease who were candidates for pituitary surgery or with persistent or recurrent Cushing's disease post surgery without having received prior pituitary irradiation. Intervention: Patients self-administered subcutaneous pasireotide 600 microg twice daily for 15 days. Main Outcome Measure: Normalization of UFC levels after 15 days of treatment.
Results: Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom 5 (17%) had normal UFC levels (responders), after 15 days of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 days of treatment. Responders appeared to have higher pasireotide exposure than non-responders.
Conclusions: Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing's disease during the treatment period of 15 days, with direct effects on adrenocorticotropin release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.
Pub Type(s) JOURNAL ARTICLE
PubMed ID 18957506