pasireotide and Malignant-Carcinoid-Syndrome

Carcinoid crisis is a life-threatening syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In the era of booming anti-tumor therapeutics, this has become more important since associated stresses can trigger carcinoid crisis. Somatostatin analogues (SSTA) have been recommended for prophylactic administration before intervention procedures for functioning NETs. However, the efficacy is still controversial. The aim of this article is to review efficacy of SSTA for preventing carcinoid crisis.. PubMed, Cochrane Controlled trials Register, and EMBASE were searched using 'carcinoid crisis' as a search term combining terms with 'somatostatin'; 'octreotide'; 'lanreotide' and 'pasireotide' until December 2013.. Twenty-eight articles were retrieved with a total of fifty-three unique patients identified for carcinoid crisis. The most common primary sites of NETs were the small intestine and respiratory tract. The triggering factors for carcinoid crisis included anesthesia/ surgery (63.5%), interventional therapy (11.5%), radionuclide therapy (9.6%), examination (7.7%), medication (3.8%), biopsy (2%) and spontaneous (2%). No randomized controlled trials (RCTs) were identified and two case-control studies were included to assess the efficacy of SSTA for preventing carcinoid crisis by meta-analysis. The overall pooled risk of perioperative carcinoid crisis was similar despite the prophylactic administration of SSTA (OR 0.44, 95% CI: 0.14 to 1.35, p=0.15).. SSTA was not helpful for preventing carcinoid crisis based on a meta-analysis of retrospective studies. Attentive monitoring and careful intervention are essential. Future studies with better quality are needed to clarify any effect of SSTA for preventing carcinoid crisis.

Topics: Humans; Intestine, Small; Malignant Carcinoid Syndrome; Neuroendocrine Tumors; Octreotide; Peptides, Cyclic; Respiratory System; Somatostatin

Neuroendocrine tumors (NETs) are relatively rare neoplasms that often present as diagnostic dilemmas due to obscure or non-specific symptoms. The ability of carcinoid tumors to cause clinical symptoms by secretion of hormones or biogenic amines is best recognised in the form of the carcinoid syndrome. Although generally slow growing, a significant minority demonstrate aggressive tumor growth. Ten-twenty percent of pancreatic NETs may be associated with hereditary disorders such as multiple endocrine neoplasia-1 (MEN-1) and less frequently, Von Hippel Lindau, which should be considered in the investigation and management of these patients. A small percentage of NETs are associated with co-existing synchronous non-carcinoid neoplasm. The aim of this paper was to review the optimal management in patients with NETs. The therapeutic options which are reviewed, including the use of somatostatin analogues, the role of surgery, the use of chemotherapy, biotherapy using interferon, peptide receptor targeted therapy. In addition, the challenging interventional management of liver metastases is discussed, including the role of hepatic-artery embolization, radiofrequency ablation and the place of orthotoptic liver transplantation in selected patients. Authors have focused on the newest therapeutic modalities, e.g., radionuclide peptide receptor targeted therapy with Yttrium-90 and Lutetium-177, the newest somatostatin analogues such as pasireotide and angiogenic inhibitors. In conclusion, with the increasing number of investigative procedures and therapeutic options available to diagnose and treat carcinoid tumors, it is vital to have a multidisciplinary approach. Furthermore, additional scientific research and controlled clinical trials are needed to determine the efficacy of the many treatment options, which for these rare tumors can only be achieved by collaboration.

Topics: Angiogenesis Inhibitors; Biochemistry; Carcinoid Tumor; Embolization, Therapeutic; Gastrinoma; Hepatic Artery; Humans; Insulinoma; Liver Transplantation; Malignant Carcinoid Syndrome; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Patient Selection; Receptors, Peptide; Somatostatin; Vipoma; von Hippel-Lindau Disease

Pasireotide (SOM230), a novel multireceptor ligand somatostatin analog (SSA), binds with high affinity to four of the five somatostatin receptor subtypes (sst1-3, 5). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics profiles of pasireotide long-acting release (LAR) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor (GEP NET) refractory to other SSAs.. In this randomized, multicenter, open-label, phase II study, patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were randomly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20, 40, or 60 mg once every 28 days for 3 months.. Forty-two patients received pasireotide LAR. Adverse events were reported by 34 (81 %) patients, with the most frequently reported including diarrhea, fatigue, abdominal pain, and nausea. Mean fasting glucose levels were increased compared with baseline at all points throughout the study. After the third injection of pasireotide LAR, the median trough plasma concentrations on day 84 were 4.82, 12.0, and 19.7 ng/mL in the 20-, 40-, and 60-mg treatment groups, respectively. Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections (accumulation ratios were approximately 1 from all dose levels).. This study demonstrated that a new, once-monthly, intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET. Steady state levels of plasma pasireotide were achieved after three injections.

Topics: Blood Glucose; Chemistry, Pharmaceutical; Defecation; Delayed-Action Preparations; Diarrhea; Endpoint Determination; Female; Humans; Male; Malignant Carcinoid Syndrome; Middle Aged; Neuroendocrine Tumors; Somatostatin