PURPOSE: A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushing's disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control. METHODS: The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed. RESULTS: Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3-6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 μg daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient. CONCLUSIONS:Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.
RCT Entities:
PURPOSE: A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushing's disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control. METHODS: The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed. RESULTS: Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3-6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 μg daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient. CONCLUSIONS: Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.
Authors: Richard A Feelders; Christiaan de Bruin; Alberto M Pereira; Johannes A Romijn; Romana T Netea-Maier; Ad R Hermus; Pierre M Zelissen; Ramona van Heerebeek; Frank H de Jong; Aart-Jan van der Lely; Wouter W de Herder; Leo J Hofland; Steven W Lamberts Journal: N Engl J Med Date: 2010-05-13 Impact factor: 91.245
Authors: Leo J Hofland; Joost van der Hoek; Richard Feelders; Maarten O van Aken; Peter M van Koetsveld; Marlijn Waaijers; Diana Sprij-Mooij; Christian Bruns; Gisbert Weckbecker; Wouter W de Herder; Albert Beckers; Steven W J Lamberts Journal: Eur J Endocrinol Date: 2005-04 Impact factor: 6.664
Authors: Rosario Pivonello; Maria Cristina De Martino; Paolo Cappabianca; Monica De Leo; Antongiulio Faggiano; Gaetano Lombardi; Leo J Hofland; Steven W J Lamberts; Annamaria Colao Journal: J Clin Endocrinol Metab Date: 2008-10-28 Impact factor: 5.958
Authors: Christiaan de Bruin; Alberto M Pereira; Richard A Feelders; Johannes A Romijn; Ferdinand Roelfsema; Diane M Sprij-Mooij; Maarten O van Aken; Aart-Jan van der Lelij; Wouter W de Herder; Steven W J Lamberts; Leo J Hofland Journal: J Clin Endocrinol Metab Date: 2009-01-13 Impact factor: 5.958
Authors: R Attanasio; A Mainolfi; F Grimaldi; R Cozzi; M Montini; C Carzaniga; S Grottoli; L Cortesi; M Albizzi; R M Testa; L Fatti; D De Giorgio; C Scaroni; F Cavagnini; P Loli; G Pagani; E Ghigo Journal: J Endocrinol Invest Date: 2008-08 Impact factor: 4.256
Authors: M Boscaro; J Bertherat; J Findling; M Fleseriu; A B Atkinson; S Petersenn; J Schopohl; P Snyder; G Hughes; A Trovato; K Hu; M Maldonado; B M K Biller Journal: Pituitary Date: 2014-08 Impact factor: 4.107
Authors: L Trementino; M Zilio; G Marcelli; G Michetti; M Barbot; F Ceccato; M Boscaro; C Scaroni; G Arnaldi Journal: Endocrine Date: 2014-12-11 Impact factor: 3.633