Pasireotide

OBJECTIVE: This study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing's disease (CD). STUDY DESIGN: This is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated...

BACKGROUND: In patients with kidney or hepatic diseases, an increment of circulating pasireotide is also expected. Therefore, this open-label, phase I study aimed to evaluate the pharmacokinetic profiles and safety of subcutaneous (SC) and long-acting release (LAR) intramuscular injections of pasireotide in male Taiwanese volunteers who are hyperendemic hepatitis B/C and chronic kidney disease (CKD). METHODS: A total of 45 male volunteers were randomized to receive one of nine treatment sequences, involving a single subcutaneous injection of 300, 600, or 900 μg pasireotide, a multiple SC injection of the same dosage of pasireotide [300, 600, or 900 μg, twice daily (b...

PURPOSE: To evaluate the impact of pasireotide (PAS) therapy on hormonal and glycometabolic outcome in patients with acromegaly previously treated with combination medical therapies or unconventional dosages of first-generation somatostatin receptor ligands (fg-SRLs). METHODS: Retrospective study carried out in two referral centers for pituitary diseases. Twenty-one acromegalic patients were switched to PAS (12 had biochemical control, 9 were uncontrolled). Data were collected after 3- and 6-months PAS treatment, and at the last available visit (median 35 months)...

Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly cabergoline, is considered the primary therapy for these patients. Prolactin normalization is achieved in 80-90% of prolactinomas treated with cabergoline. Patients resistant to the standard dose can escalate the dose of cabergoline up to the maximum tolerated dose. The expression of dopamine (D2) receptors and dopamine affinity is decreased in aggressive and resistant prolactinomas...

PURPOSE: Cushing's disease (CD) results from autonomous adrenocorticotropic hormone (ACTH) secretion by corticotroph adenomas, leading to excessive cortisol production, ultimately affecting morbidity and mortality. Pasireotide is the only FDA approved tumor directed treatment for CD, but it is effective in only about 25% of patients, and is associated with a high rate of hyperglycemia. Neuromedin B (NMB), a member of the bombesin-like peptide family, regulates endocrine secretion and cell proliferation...

PURPOSE: The specific indications of somatostatin analogs (SSAs) in patients with neuroendocrine tumor (NET) emerged over the time. The objective of this review is to summarize and discuss the most relevant data concerning long-acting SSAs in NET. METHODS: A narrative review was performed including publications focusing on therapy with the long-acting octreotide, lanreotide, and pasireotide in patients with NET. RESULTS: Long-acting SSAs confirm to be a manageable and widely used tool in patients with NET...

Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical diagnosis is often delayed by several years due to the slowly progressive onset of symptoms. There are multiple clinical criteria that define acromegaly: dysmorphic syndrome of insidious onset, symptoms related to the pituitary tumor (headaches, visual disorders), general signs (sweating, carpal tunnel syndrome, joint pain, etc.), complications of the disease (musculoskeletal, cardiovascular, pneumological, dental, metabolic comorbidities, thyroid nodules, colonic polyps, etc...

Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks in the pancreatic ductal system, leading to various complications such as abscesses, delayed gastric emptying, and hemorrhage. Severe cases present with sepsis or organ failure, dramatically increasing mortality and morbidity. Risk factors include smoking, high BMI, male gender, age, and surgery-related factors like prolonged operation time and non-ligation of the main pancreatic duct...

Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords "somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula" was made...

Pasireotide long-acting release is effective in achieving biochemical control and reducing tumour volume in patients with acromegaly inadequately controlled by first-line therapy. As part of a long-term, real-world study at our centre, 20 of 50 patients receiving pasireotide benefited from a reduction in pasireotide dose. Pasireotide reduced insulin-like growth factor I (IGF-I) levels to below the upper limit of the normal range, with some patients responding within 1-3 months of treatment (n=11) and others after ≥4 months (n=9)...

Transsphenoidal surgery is the first-line treatment for most functioning pituitary neuroendocrine tumors(PitNETs). Medical therapies are usually chosen for patients with residual or refractory tumors after surgery or contraindications to surgery. Dopamine agonists(DA)are the first-line treatment for prolactinomas. Somatostatin analogs are the first line of therapy for GH- and TSH-producing PitNETs. In severe hypercortisolemia due to ACTH-producing PitNETs, adrenal enzyme inhibitors such as 11β-hydroxylase inhibitors should be started immediately, as marked hypercortisolemia leads to serious opportunistic infections...

Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur...

Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It was first reported in 1954, and the classical symptoms are diarrhoea, flushing and abdominal pain. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. Therefore, the focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patient's quality of life...

OBJECTIVE: Hyperintensity signal in T2-weighted magnetic resonance imaging (MRI) has been related to better therapeutic response during pasireotide treatment in acromegaly. The aim of the study was to evaluate T2 MRI signal intensity and its relation with pasireotide therapeutic effectiveness in real-life clinical practice. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective multicentre study including acromegaly patients treated with pasireotide. Adenoma T2-weighted MRI signal at diagnosis was qualitatively classified as iso-hyperintense or hypointense...

In elective pancreatic surgery, somatostatin-analogues pasireotide and octreotide are variably used to reduce postoperative complications, but knowledge on their role in pancreas transplantation is limited. This study compared pasireotide and octreotide for their association with complications after simultaneous pancreas-kidney transplantation (SPK). This retrospective study included consecutive patients undergoing SPK's from July 2013 to July 2022. Between July 2013 and April 2020, octreotide was administered 0...

CONTEXT: Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control. OBJECTIVE: As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed. METHODS: A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008)...

Somatotroph adenomas are usually controlled with standard therapy, which can include surgery, medical treatment and radiotherapy. Some tumors have a more aggressive behavior and are refractory to standard therapy. In this review, we summarize the phenotype of these tumors and the current options for their management.

PURPOSE: Clinical control of corticotroph tumors is difficult to achieve since they usually persist or relapse after surgery. Pasireotide is approved to treat patients with Cushing's disease for whom surgical therapy is not an option. However, Pasireotide seems to be effective only in a sub-set of patients, highlighting the importance to find a response marker to this approach. Recent studies demonstrated that the delta isoform of protein kinase C (PRKCD) controls viability and cell cycle progression of an in vitro model of ACTH-secreting pituitary tumor, the AtT-20/D16v-F2 cells...

Acromegaly is a rare endocrine disorder, which despite the recent advances in diagnosis and management, remains a significant burden in terms of morbidity and mortality for patients because of the frequent aggressive evolution and lack of response to available first-line pharmacological therapy. A switch from the classical "trial and error" management to a personalized therapy approach has been proposed through early identification of biomarkers that could predict treatment response and biological behavior...

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