Pasireotide (SOM230) Demonstrates Efficacy and Safety in Patients with Acromegaly: A Randomized, Multicenter, Phase II Trial

Petersenn, Stephan; Schopohl, Jochen; Barkan, Ariel; Mohideen, Pharis; Colao, Annamaria; Abs, Roger; Buchelt, Alexandra; Ho, Yu-Yun; Hu, Ke; Farrall, Andrew; Melmed, Shlomo; Biller, Beverly M. K.

doi:10.1210/jc.2009-2272

Cited by 185 publications

(129 citation statements)

References 18 publications

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“…Similar rates of biochemical control (27%) were reported with pasireotide after 3 months of treatment; 39% of the cases also had a significant (O20%) decrease in pituitary tumor volume (Petersenn et al 2010). In the study of Colao et al (2014), almost 80% of the cases treated for 1 year with either pasireotide or OCT LAR achieved a significant tumor decrease (mean reduction 40%), both postsurgical and de novo treated cases.…”

Section: Medical Treatmentsupporting

confidence: 62%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.

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Section: Medical Treatmentsupporting

confidence: 62%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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“…Thus, DG3173 may prove to be at least as efficient, as well as even more specific as already existing SSA. In contrast, another new SSA SOM230 with a broad range of sst binding has been shown to substantially inhibit insulin secretion in vivo (14,20,39,40).…”

Section: Discussionmentioning

confidence: 98%

“…In one-third of acromegalic patients, who do not respond to Octreotide, there is diminished expression of sst2A, but persistent sst5 expression (13). SOM230 (Pasireotide), a new multiligand SSA with binding to all sst except to sst4, is currently investigated in clinical trials (14,15,16,17,18,19). Nevertheless, its negative effects on glucose tolerance are even more pronounced than with Octreotide (14,20).…”

Section: Introductionmentioning

confidence: 99%

“…SOM230 (Pasireotide), a new multiligand SSA with binding to all sst except to sst4, is currently investigated in clinical trials (14,15,16,17,18,19). Nevertheless, its negative effects on glucose tolerance are even more pronounced than with Octreotide (14,20). On the other hand, BIM-23A760 (Dopastatin), a chimeric molecule directed towards somatostatin (mainly sst2 and sst5) and dopamine D2 receptors (21,22,23), suppresses GH in vitro but was ineffective when applied to acromegalic patients in clinical trials (press release 15 Dec 2010, Ipsen Pharma).…”

Section: Introductionmentioning

confidence: 99%

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DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours

Plöckinger

Hoffmann²,

Geese³

et al. 2012

European Journal of Endocrinology

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Objective: Somatostatin analogues (SSA) reduce autonomous GH secretion by activating somatostatin receptors (sst) 2 and 5 in 50-60% of acromegalic patients. However, by inhibiting insulin secretion these SSA reduce glucose tolerance. DG3173 is a novel SSA with additional binding to sst4 and low insulin-suppressing activity. We investigated the effect of DG3173, including its relation to specific tumour characteristics, on GH secretion in human somatotroph adenoma cell cultures (hSA) in comparison with Octreotide. Methods: Twenty-seven hSA were characterised immunohistochemically for their hormone-and sstexpression, granularity and pre-surgical therapy with SSA. GH was determined in supernatants of hSA treated with DG3173 or Octreotide in time-(nZ6) and dose-response (nZ21) experiments. A positive response was defined as GH suppression to below 80% of baseline. Results: In the dose-response experiments DG3173 suppressed GH secretion in more adenomas than Octreotide (10/21 vs 5/21), including 38% (6/16) of Octreotide non-responders. In responders the extent of GH suppression and IC 50 were comparable for both SSA. The response-rate of both SSA was higher in monohormonal vs bihormonal adenomas, yet GH declined similarly in both groups. Neither pre-surgical SSA (nZ6) nor tumour morphology was related to the GH response. However, semiquantitative analysis indicated a small but significant negative correlation between the GH response to Octreotide and the immunoreactivity scores of sst2 expression. Conclusions: DG3173 equalled Octreotide in suppressing GH secretion in hSA. Since DG3173 suppressed GH in some Octreotide-non-responsive adenomas, its clinical effectiveness will be worth testing. Moreover, its reduced insulin-suppressive potency would make it a valuable alternative to Octreotide.

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“…18,28 However, lanreotide and octreotide differ in their mode of administration (long-acting lanreotide formulations are available in ready-to-use prefilled syringes that are injected subcutaneously; long-acting octreotide formulations require reconstitution before being injected intramuscularly), which might influence patient convenience (VLQ). 24 At least two other SRL formulations are currently undergoing clinical development for acromegaly: pasireotide, which has a different somatostatin receptor-binding profile; 29 and oral octreotide. 30 …”

Section: Somatostatin Receptor Ligandsmentioning

confidence: 99%

Expert consensus document: A consensus on the medical treatment of acromegaly

et al. 2014

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| In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus.

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Pasireotide (SOM230) Demonstrates Efficacy and Safety in Patients with Acromegaly: A Randomized, Multicenter, Phase II Trial

Abstract: Pasireotide is a promising treatment for acromegaly. Larger studies of longer duration evaluating the efficacy and safety of pasireotide in patients with acromegaly are ongoing.

Cited by 185 publications

References 18 publications

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours

Expert consensus document: A consensus on the medical treatment of acromegaly

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