Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease

Feelders, Richard A; Bruin, Christiaan de; Pereira, Alberto M.; Romijn, Johannes A.; Netea‐Maier, Romana T.; Hermus, A.R.M.M.; Zelissen, Pierre; Heerebeek, Ramona van; Jong, Frank H. de; Lely, Aart-Jan van der; Herder, Wouter W. de; Hofland, Leo J.; Lamberts, Steven W. J.

doi:10.1056/nejmc1000094

Cited by 233 publications

(146 citation statements)

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“…Preliminary results showed a limited remission rate of only 29% with pasireotide monotherapy, with disturbance of glucose homeostasis as the main adverse event (13). With these different pharmacological approaches, a combination of several medications often seems necessary to adequately control CD (13,40). In our study, complete remission was achieved in 48 patients with mitotane monotherapy.…”

Section: Discussionmentioning

confidence: 56%

“…Another pharmacologic agent, pasireotide, has been investigated in a phase III randomized double-blind trial comparing two doses in CD (14). Preliminary results showed a limited remission rate of only 29% with pasireotide monotherapy, with disturbance of glucose homeostasis as the main adverse event (13). With these different pharmacological approaches, a combination of several medications often seems necessary to adequately control CD (13,40).…”

Section: Discussionmentioning

confidence: 99%

“…The main pharmacotherapeutic treatments for CD are adrenal-blocking drugs such as metyrapone, ketoconazole, and 1,ortho-1, para'-dichloro-diphényl-dichloro-ethane (o,p'DDD), also termed mitotane (3,8,9,10). Other drugs that directly target ACTH secretion have recently been developed but induce only limited and/or transient remission (11,12,13,14) of CD.…”

Section: Introductionmentioning

confidence: 99%

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Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Baudry

Coste

Khalil

et al. 2012

European Journal of Endocrinology

164

118

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Context: Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first-or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD. Objective: Evaluation of the efficacy and tolerance of mitotane in CD patients. Design and setting: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. Main outcome measure: Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC). Results: Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5G8.9 mg/l, with a mean daily dose of 2.6G1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P!0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), PZ0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery. Conclusion: Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Baudry

Coste

Khalil

et al. 2012

European Journal of Endocrinology

164

118

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“…It is noteworthy that short-term results are not always predictive of long-term outcomes. Several case reports also suggest that there is no loss of efficacy after long-term therapy with pasireotide [83][84][85], although more data are needed.…”

Section: Pasireotide and Pasireotide Larmentioning

confidence: 99%

“…Feelders et al [83] conducted an 80-day study where pasireotide was initially administered as monotherapy, and cabergoline and low-dose ketoconazole were sequentially added at 4 and 8 weeks, respectively, as normalisation of urinary cortisol levels was achieved. This approach achieved normalisation in 90% of patients.…”

Section: Pasireotide and Pasireotide Larmentioning

confidence: 99%

Emerging drugs for Cushing’s disease

Guelho

Grossman

2015

Expert Opinion on Emerging Drugs

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Hormones, 2. Peptides and Proteins: Hypothalamic–Pituitary and Calcitropic Hormones

Sandow

2013

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Hypothalamic and Pituitary Hormones 2.1. The Hypothalamic–Pituitary System 2.2. Pituitary Hormone Preparations 2.2.1. Thyrotropin‐Releasing Hormone (TRH) 2.2.2. Thyrotropin (TSH) 2.2.3. Luteinizing Hormone Releasing Hormone (LHRH, GnRH) 2.2.4. Luteinizing Hormone (LH), Follitropin (FSH), Human Chorionic Gonadotropin (HCG) 2.3. Growth Hormone and Prolactin Regulation 2.3.1. Growth‐Hormone‐Releasing Hormone 2.3.2. Somatostatin 2.3.3. Growth Hormone 2.3.4. Prolactin and Human Placental Lactogen (HPL) 2.4. The Melanocortin System 2.4.1. Corticotropin‐Releasing Hormone (CRH) 2.4.2. Corticotropin (ACTH) 2.4.3. Melanocyte‐Stimulating Hormone (MSH) 2.4.4. Melanocortins 2.4.5. Proopiomelanocortin (POMC) Processing 2.5. New Hypothalamic–Pituitary Peptides 2.6. Neurohypophyseal Peptides 2.6.1. Vasopressin 2.6.2. Oxytocin 3. Calcium‐Regulating Hormones 3.1. Calcitonin 3.2. Parathormone

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Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease

Abstract: Please be advised that this information was generated on 2020-07-16 and may be subject to change.T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 362;19 nejm.

Cited by 233 publications

References 5 publications

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Emerging drugs for Cushing’s disease

Hormones, 2. Peptides and Proteins: Hypothalamic–Pituitary and Calcitropic Hormones

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