Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

Kvols, Larry K.; Öberg, Kjell; O'Dorisio, Thomas M.; Mohideen, Pharis; Herder, Wouter W. de; Arnold, R.; Hu, Ke; Zhang, Yilong; Hughes, G.; Anthony, Lowell; Wiedenmann, Bertram

doi:10.1530/erc-11-0367

Cited by 176 publications

(127 citation statements)

References 19 publications

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“…Together, these data raise the question of its use in GEP-NETs. In a phase II clinical trial, pasireotide has been shown to control symptoms related to carcinoid syndrome in 27% of patients with NETs who were resistant to octreotide (Kvols et al 2012). However, the effects of pasireotide in comparison to octreotide on tumor secretion and proliferation and its relationship to WHO grades, sst expression profile, and sst trafficking in GEP-NETs remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures

Mohamed¹,

Blanchard²,

Albertelli³

et al. 2014

Endocrine Related Cancer

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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) raise difficult therapeutic problems despite the emergence of targeted therapies. Somatostatin analogs (SSA) remain pivotal therapeutic drugs. However, the tachyphylaxis and the limited antitumoral effects observed with the classical somatostatin 2 (sst 2 ) agonists (octreotide and lanreotide) led to the development of new SSA, such as the pan sst receptor agonist pasireotide. Our aim was to compare the effects of pasireotide and octreotide on cell survival, chromogranin A (CgA) secretion, and sst 2 phosphorylation/trafficking in pancreatic NET (pNET) primary cells from 15 tumors. We established and characterized the primary cultures of human pancreatic tumors (pNETs) as powerful preclinical models for understanding the biological effects of SSA. At clinically relevant concentrations (1-10 nM), pasireotide was at least as efficient as octreotide in inhibiting CgA secretion and cell viability through caspase-dependent apoptosis during short treatments, irrespective of the expression levels of the different sst receptors or the WHO grade of the parental tumor. Interestingly, unlike octreotide, which induces a rapid and persistent partial internalization of sst 2 associated with its phosphorylation on Ser341/343, pasireotide did not phosphorylate sst 2 and induced a rapid and transient internalization of the receptor followed by a persistent recycling at the cell surface. These results provide the first evidence, to our knowledge, of striking differences in the dynamics of sst 2 trafficking in pNET cells treated with the two SSAs, but with similar efficiency in the control of CgA secretion and cell viability.

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Section: Introductionmentioning

confidence: 99%

Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures

Mohamed¹,

Blanchard²,

Albertelli³

et al. 2014

Endocrine Related Cancer

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“…When no symptomatic control is achieved, another option of treatment would be the novel multireceptor-targeted somatostatin analogue pasireotide (previously known as SOM230). In a recently published phase II, open-label, multicentre study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhoea/flushing) were inadequately controlled by octreotide LAR, pasireotide 600-900 μg given subcutaneously reduced daily flushing episodes from 4.9 ± 4.1 at baseline to 1.0 ± 0.8 post-treatment and was effective in controlling the symptoms of diarrhoea and flushing in 27% of patients with advanced NETs who were no longer responsive to octreotide LAR (54). The use of octreotide before invasive procedures is also important to prevent a carcinoid crisis.…”

Section: Carcinoid Syndromementioning

confidence: 97%

MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

Huguet

Grossman

2017

European Journal of Endocrinology

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Objective: Flushing can be defined as a sensation of warmth accompanied by erythema that most commonly is seen on the face and which occurs in episodic attacks. Such a problem can be clinically problematic, since many conditions and drugs can be related to flushing, and while often there appears to be no underlying organic disease, it is important to exclude disorders since they may be life-threatening conditions. Design and methods: We performed a search in MEDLINE using the terms 'flushing' in combination with 'carcinoid syndrome', 'pheochromocytoma', 'mastocytosis', 'menopausal hot flush' and 'treatment'. European and American guidelines relating to neuroendocrine tumours, mastocytosis and menopause were reviewed. Results: In this review, we discuss the main causes of flushing and propose an algorithm based on pathogenesis, which can be used to guide the clinical evaluation process. We also review recent significant developments in the assessment and treatment of the carcinoid syndrome and menopausal hot flushes, which should guide the clinical practice regarding this common but sometimes confusing condition. Conclusions: When evaluating flushing, a precise systematic approach is needed to exclude potentially serious underlying causes, although despite this, the cause of the disorder is not always found. If symptoms are not progressive, the patient should be advised about its apparently benign nature in order to avoid unnecessary studies or initiating treatments of minimal benefit.

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“…The search uncovered eleven relevant randomized prospective studies [9][10][11][12][13][14][15][16][17][18][19] , sixteen nonrandomized prospective studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] , and thirteen retrospective studies [36][37][38][39][40][41][42][43][44][45][46][47][48] . Where multiple reports and abstracts were published for a single trial or study, only the most recent full publication was included, unless other reports contained data that were not available in the most recent publication.…”

Section: Primary Literaturementioning

confidence: 99%

Systemic Therapy in Incurable Gastroenteropancreatic Neuroendocrine Tumours: A Clinical Practice Guideline

Singh¹,

Sivajohanathan

Asmis

et al. 2017

Current Oncology

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PurposeThe purpose of the present review was to determine which antineoplastic systemic therapy is most effective in improving clinical outcomes for patients with incurable gastroenteropancreatic neuroendocrine tumours (nets).Methods A systematic search (2008-2016) of the literature in the medline and embase databases and the Cochrane Database of Systematic Reviews was conducted; abstracts from the American Society of Clinical Oncology, the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, the European Society for Medical Oncology, the European Cancer Congress, the European Neuroendocrine Tumor Society, and the North American Neuroendocrine Tumor Society were reviewed. Draft recommendations were created, and a comprehensive review process was undertaken. Outcomes-including progression-free survival (pfs), overall survival, objective response rate, adverse events, and quality of life-were extracted from each of the studies. ResultsEleven randomized controlled trials (rcts), sixteen nonrandomized prospective studies, and thirteen retrospective studies met the inclusion criteria.Conclusions Patients with well-or moderately-differentiated pancreatic nets (pnets) should receive targeted therapy (that is, everolimus or sunitinib), and patients with non-pnets should be offered either targeted therapy (that is, everolimus) or somatostatin analogues (ssas-that is, octreotide long-acting release or lanreotide). Evidence from two phase iii trials demonstrated a significant pfs benefit for patients with pnets. For patients with non-pnets, the evidence comes from subgroup analyses of rcts, as well as from a planned interim analysis. Although the evidence has limitations, the rarity of the disease, coupled with the difficulty of conducting methodologically sound trials in the affected population, means that treatment decisions have to make use of the best available evidence. Because of insufficient evidence for both pnets and non-pnets, no evidence-based recommendation can be made for or against other types of targeted therapy, other ssas, chemotherapy, or combination therapy.

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Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

Cited by 176 publications

References 19 publications

Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures

Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures

MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

Systemic Therapy in Incurable Gastroenteropancreatic Neuroendocrine Tumours: A Clinical Practice Guideline

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