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Treatment of Pituitary-Dependent Cushing’s Disease with the Multireceptor Ligand Somatostatin Analog Pasireotide (SOM230): A Multicenter, Phase II Trial

Division of Endocrinology (M.B.), Polytechnic University of Marche, 60126 Ancona, Italy; Seattle Pituitary Center (W.H.L.), Swedish Neurosciences Institute, Seattle, Washington 98122; Regional Centre for Endocrinology and Diabetes (B.A.), Royal Victoria Hospital, Belfast BT12 6BA, United Kingdom; Oncology Clinical Development (J.E.G., C.H.D., K.H., Y.W.), Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07932; Division of Endocrinology (S.P.), Medical Center, University of Essen, 45122 Essen, Germany; Medizinische Klinik Innenstadt Klinikum der Universität München (M.R.), 80336 München, Germany; University of Pennsylvania (P.S.), Philadelphia, Pennsylvania 19104; Service d’Endocrinologie (A.T.), Centre Hospitalier Universitaire Bordeaux, Haut Lévêque, 33075 Pessac, France; Massachusetts General Hospital (B.M.K.B.), Boston, Massachusetts 02114; Midwest Endocrinology Associates (J.F.), Milwaukee, Wisconsin 53215; Cedars-Sinai Pituitary Center (S.M.), Los Angeles, California 90048; Department of Medicine (P.U.F.), Division of Endocrinology, Columbia University, New York, New York 10027; Department of Endocrinology (A.B.G.), St. Bartholomew’s Hospital, EC1M 6BQ London, United Kingdom; Department of Medicine (L.A.F.), Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, Illinois 60637; and Center for Rare Adrenal Diseases (J.B.), Department of Endocrinology, Institut National de la Santé et de la Recherche Médicale Unit 567, Paris-Descartes University, Cochin Hospital, 75014 Paris, France

Address all correspondence and requests for reprints to: Jérôme Bertherat, Institut National de la Santé et de la Recherche Médicale Unit 567, Institut Cochin, Paris-Descartes University, Assistance Publique-Hôpitaux de Paris, Center for Rare Adrenal Disease, Department of Endocrinology, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail: jerome.bertherat{at}cch.aphp.fr.

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: Our objective was to evaluate the short-term efficacy of the novel multireceptor ligand somatostatin analog pasireotide in patients with de novo, persistent, or recurrent Cushing’s disease.

Design: We conducted a phase II, proof-of-concept, open-label, single-arm, 15-d multicenter study.

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 after surgery without having received prior pituitary irradiation.

Intervention: Patients self-administered sc pasireotide 600 µg twice daily for 15 d.

Main Outcome Measure: Normalization of urinary free cortisol (UFC) levels after 15 d treatment was the main outcome measure.

Results: Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom five (17%) had normal UFC levels (responders), after 15 d of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment. Responders appeared to have higher pasireotide exposure than nonresponders.

Conclusions: Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing’s disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.

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