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Interactive Cardiovascular and Thoracic... Oct 2021A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was how efficacious are Octreotide and Somatostatin in...
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was how efficacious are Octreotide and Somatostatin in the management of chylothorax in congenital cardiac surgical patients. Altogether >55 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The comparative data on LOS and chylothorax duration are mixed though interpretation is difficult since Octreotide has been instituted belatedly from the onset of chylothorax in multiple instances. There is also preliminary evidence to suggest that responders to Somatostatin and Octreotide are affected by single-ventricle physiology and CVP levels. Meanwhile, non-responders tend to have higher mortality and may merit earlier surgical intervention. The included studies thus far have significant limitations such as low-level evidence study design, selection bias, variability in duration and dosage of therapy and heterogenous comparative arms. Notwithstanding these limitations, Octreotide has shown to be an useful adjunct treatment in reducing chylothorax volume especially in patients with higher output chylothorax (>40 ml/kg/h) after the failure of conservative management.
Topics: Cardiac Surgical Procedures; Chylothorax; Humans; Octreotide; Somatostatin; Treatment Outcome
PubMed: 34000045
DOI: 10.1093/icvts/ivab155 -
BMJ (Clinical Research Ed.) May 1994
Topics: Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Octreotide; Randomized Controlled Trials as Topic; Somatostatin
PubMed: 7912595
DOI: 10.1136/bmj.308.6941.1381 -
Early Human Development Jul 2015Octreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in...
BACKGROUND
Octreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in hospitalized infants has not been described; we sought to fill this information gap.
METHODS
We identified all infants exposed to at least 1 dose of octreotide from a cohort of 887,855 infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. We collected laboratory and clinical information while infants were exposed to octreotide and described the frequency of baseline diagnoses, laboratory abnormalities, and clinical adverse events (AEs).
RESULTS
A total of 428 infants received 490 courses of octreotide. The diagnoses most commonly associated with octreotide use were chylothorax (50%), pleural effusion (32%), and hypoglycemia (22%). The most common laboratory AEs that occurred during exposure to octreotide were thrombocytopenia (47/1000 infant-days), hyperkalemia (21/1000 infant-days), and leukocytosis (20/1000 infant-days). Hyperglycemia occurred in 1/1000 infant-days and hypoglycemia in 3/1000 infant-days. Hypotension requiring pressors (12%) was the most common clinical AE that occurred during exposure to octreotide. Necrotizing enterocolitis was observed in 9/490 (2%) courses, and death occurred in 11 (3%) infants during octreotide administration.
CONCLUSION
Relatively few AEs occurred during off-label use of octreotide in this cohort of infants. Additional studies are needed to further evaluate the safety, dosing, and efficacy of this medication in infants.
Topics: Antineoplastic Agents, Hormonal; Chylothorax; Female; Hospitalization; Humans; Hypoglycemia; Hypotension; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Octreotide; Off-Label Use; Pleural Effusion; Thrombocytopenia
PubMed: 25968047
DOI: 10.1016/j.earlhumdev.2015.04.008 -
Gut 1994Persistent, refractory diarrhoea continues to be an important clinical problem. The mechanisms involved are associated with reduced intestinal absorption and increased... (Review)
Review
Persistent, refractory diarrhoea continues to be an important clinical problem. The mechanisms involved are associated with reduced intestinal absorption and increased intestinal secretion. Reduced intestinal absorption can result from small intestinal resection or from disorders in which there is damage to the small intestine. Motility disorders may also impair absorptive function. The rationale for using octreotide in refractory diarrhoea, intestinal motility disorders, and fistulae relates to its ability to promote intestinal absorption and inhibit gastric, pancreatic, and intestinal secretion. Several clinical studies in patients with short bowel syndrome have reported a reduction of intestinal output in patients taking octreotide compared with controls. Additionally, a number of studies have shown that octreotide improves secretory diarrhoea resulting from neuroendocrine tumours, intestinal infections in AIDS patients, and intestinal graft v host disease. Octreotide may be of use in patients suffering from intestinal motility disorders such as those associated with systemic sclerosis. Octreotide may also be of value in promoting closure of gastrointestinal and pancreatic fistulae.
Topics: Chronic Disease; Diarrhea; Humans; Intestinal Absorption; Intestinal Mucosa; Octreotide
PubMed: 8206397
DOI: 10.1136/gut.35.3_suppl.s5 -
Gut 1994Bleeding from oesophageal varices has a high death rate. Injection sclerotherapy is the most appropriate treatment but facilities for this are not always available.... (Meta-Analysis)
Meta-Analysis
Bleeding from oesophageal varices has a high death rate. Injection sclerotherapy is the most appropriate treatment but facilities for this are not always available. Balloon tamponade and vasoactive therapy may be used as stop gap measures. Somatostatin and octreotide are therapeutic candidates for the treatment of variceal bleeding and there are several trials that have compared somatostatin and octreotide with other treatments for this condition. The results of these trials are summarised and discussed. A meta analysis of the group of trials of placebo or H2 antagonists v somatostatin or octreotide showed a significant advantage of somatostatin or octreotide in terms of efficacy, but no difference in mortality. The trials discussed seem to show that somatostatin and octreotide are at least as effective as other treatments, with the benefit of fewer adverse effects, and thus represent the best vasoactive agents. Additionally, they may have a role as adjuvant treatment to emergency sclerotherapy for active bleeders and this must be further investigated.
Topics: Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Octreotide
PubMed: 8206396
DOI: 10.1136/gut.35.3_suppl.s23 -
European Journal of Nuclear Medicine... Jul 2021The radiolabelled somatostatin analogue [Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing...
PURPOSE
The radiolabelled somatostatin analogue [Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [Lu]Lu-DOTA-TOC.
METHODS
Activity kinetics in organs and tumours after [Lu]Lu-DOTA-EB-TATE and [Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy.
RESULTS
In comparison to [Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [Lu]Lu-DOTA-TOC in 4 of 5 patients.
CONCLUSIONS
Prior to a treatment with [Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.
Topics: Evans Blue; Humans; Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Somatostatin
PubMed: 33452632
DOI: 10.1007/s00259-020-05177-z -
Journal of Nuclear Medicine : Official... Feb 2022The purpose of this study was to assess the efficacy and safety of Lu-DOTATATE in patients with somatostatin receptor (SSR)-positive lung neuroendocrine tumors (NETs)....
The purpose of this study was to assess the efficacy and safety of Lu-DOTATATE in patients with somatostatin receptor (SSR)-positive lung neuroendocrine tumors (NETs). This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with Lu-DOTATATE at 2 ENETS Centers of Excellence. Morphologic imaging (RECIST 1.1) and Ga-DOTATATE PET/CT responses were assessed at 3 mo after completion of Lu-DOTATATE. Concordance between 2 response assessment methods was evaluated by κ statistics. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on Common Terminology Criteria for Adverse Events, version 5. Of 48 patients (median age, 63 y; 13 women), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Most patients (40, 83%) received somatostatin analogs, and 10 patients (20%) had prior everolimus, chemotherapy, or both. All patients had high SSR expression (≥ modified Krenning score 3) on pretreatment Ga-DOTATATE PET/CT. Patients received a median 4 (range, 1-4) cycles of Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27 GBq (range, 6-43GBq). At a median follow-up of 42 mo, the median PFS and OS were 23 mo (95% CI, 18-28 mo) and 59 mo (95% CI, 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available Ga-DOTATATE PET/CT, response categories were partial response, 20% (95% CI, 10%-35%) and 44% (95% CI, 30%-59%); stable disease, 68% (95% CI, 52%-80%) and 44% (95% CI, 30%-59%); and progressive disease, 12% (95% CI, 5%-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and Ga-DOTATATE PET/CT, weighted κ of 0.51 (95% CI, 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on Ga-DOTATATE PET/CT had a longer OS than those with no response, NR versus 52 mo (95% CI, 28-64), hazard ratio 0.2 (95% CI, 0.1-0.6), < 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia or leukemia. In patients with advanced progressive lung NET and satisfactory SSR expression, Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Retrospective Studies
PubMed: 34049983
DOI: 10.2967/jnumed.120.260760 -
Future Oncology (London, England) Feb 2016Midgut neuroendocrine tumors (NETs) are relatively rare and remarkably heterogeneous. Although recent developments for pancreatic NETs have brought multiple new... (Review)
Review
Midgut neuroendocrine tumors (NETs) are relatively rare and remarkably heterogeneous. Although recent developments for pancreatic NETs have brought multiple new therapies to patients who need them, there has been little observed efficacy against midgut NETs. Peptide receptor radionuclide therapy utilizes somatostatin analogs conjugated to radioactive isotopes in order to deliver high doses of radiation directly to tumor cells, which express somatostatin receptors. Peptide receptor radionuclide therapy with [(177)Lu-DOTA(0),Tyr(3)]-octreotate (DOTATATE) has been reported and investigated for more than a decade, and the randomized controlled NETTER-1 study of this agent has recently been reported to show promising results. In this article, we will summarize and evaluate the rationale and existing clinical data for the activity of DOTATATE in midgut NETs, to give context for the interpretation of NETTER-1 results when they are fully available.
Topics: Antineoplastic Agents, Hormonal; Coordination Complexes; Gastrointestinal Neoplasms; Humans; Neuroendocrine Tumors; Octreotide; Radiopharmaceuticals; Treatment Outcome
PubMed: 26759064
DOI: 10.2217/fon.15.321 -
Seminars in Oncology Aug 2018Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is now approved for patients with advanced gastroenteropancreatic neuroendocrine tumors (NET), and it is... (Review)
Review
Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is now approved for patients with advanced gastroenteropancreatic neuroendocrine tumors (NET), and it is therefore important to understand the efficacy and safety of PRRT in this patient population. PRRT efficacy and safety outcomes have frequently been summarized for patient populations with gastroenteropancreatic NET, but not specifically in patients with pancreatic NET (panNET). The pivotal phase 3 trial of Lu-DOTATATE PRRT in NET was restricted to patients with a midgut primary site. No phase 3 trial data on PRRT treatment outcomes are currently available for the panNET patient population. This review presents the available evidence for panNET treatment outcomes with PRRT and demonstrates that the available data favor PRRT as a modality for this NET primary site. However, several other therapies for advanced panNET are currently available, and the sequencing and combination of PRRT with these other therapies is set to become the big challenge for the future of panNET management. Patient, tumor, and logistical factors (tumor burden, expression of somatostatin receptors, availability of PRRT, patient preferences, and concerns over long-term toxicity) need to be taken into consideration when selecting therapy.
Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radioisotopes; Stomach Neoplasms
PubMed: 30539715
DOI: 10.1053/j.seminoncol.2018.08.004 -
British Journal of Clinical Pharmacology Sep 2015The aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation. (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation.
METHODS
This was a phase I, randomized, open label study. After a single dose of octreotide immediate release (IR) 200 µg, subjects were randomized to one of eight groups to receive three monthly injections of octreotide s.c. depot A 10, 20 or 30 mg, B 30 mg, C 10, 20 or 30 mg or long acting octreotide (octreotide LAR) 30 mg.
RESULTS
One hundred and twenty-two subjects were randomized. For all depot variants, onset of octreotide release was rapid and sustained for up to 4 weeks. The relative octreotide bioavailability of depot variants vs. octreotide IR ranged from 0.68 (90% confidence interval [CI] 0.61, 0.76) to 0.91 (90% CI 0.81, 1.02) and, vs. octreotide LAR, was approximately four- to five-fold greater: 3.97 (90% CI 3.35, 4.71) to 5.27 ng ml(-1) h (90% CI 4.43, 6.27). All depot variants showed relatively rapid initial reductions of insulin-like growth factor 1 (IGF-1) compared with octreotide LAR. A trend of octreotide dose dependence was also indicated from the plasma concentrations and suppression of IGF-1. Maximum inhibition of IGF-1 at steady-state was highest for depot B and C. All depot treatments were well tolerated. The most frequent adverse events were gastrointestinal related.
CONCLUSIONS
Octreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF-1 than octreotide LAR in healthy volunteers.
Topics: Adult; Antineoplastic Agents, Hormonal; Biological Availability; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Liberation; Female; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide; Young Adult
PubMed: 26076191
DOI: 10.1111/bcp.12698