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Journal of Nuclear Medicine : Official... Jun 2016Neuroendocrine tumors (NETs) are uncommon tumors with increasing incidence and prevalence. Current reports suggest that (68)Ga-DOTATATE PET/CT imaging improves diagnosis... (Comparative Study)
Comparative Study Meta-Analysis Review
68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis.
UNLABELLED
Neuroendocrine tumors (NETs) are uncommon tumors with increasing incidence and prevalence. Current reports suggest that (68)Ga-DOTATATE PET/CT imaging improves diagnosis and staging of NETs compared with (111)In-DTPA-octreotide and conventional imaging. We performed a systematic review of (68)Ga-DOTATATE for safety and efficacy compared with octreotide and conventional imaging to determine whether available evidence supports U.S. Food and Drug Administration approval.
METHODS
Medline, EMBASE, Web of Science, and Cochrane Reviews electronic databases were searched from January 1999 to September 2015. Results were restricted to human studies comparing diagnostic accuracy of (68)Ga-DOTATATE with octreotide or conventional imaging for pulmonary or gastroenteropancreatic NET and for human studies reporting safety/toxicity for (68)Ga-DOTATATE with 10 subjects or more thought to have NETs. Direct communication with corresponding authors was attempted to obtain missing information. Abstracts meeting eligibility criteria were collected by a research librarian and assembled for reviewers; 2 reviewers independently determined whether or not to include each abstract. If either reviewer chose inclusion, the abstract was accepted for review.
RESULTS
Database and bibliography searches yielded 2,479 articles, of which 42 were eligible. Three studies compared the 2 radiopharmaceuticals in the same patient, finding (68)Ga-DOTATATE to be more sensitive than octreotide. Nine studies compared (68)Ga-DOTATATE with conventional imaging. (68)Ga-DOTATATE estimated sensitivity, 90.9% (95% confidence interval, 81.4%-96.4%), and specificity, 90.6% (95% confidence interval, 77.8%-96.1%), were high. Five studies were retained for safety reporting only. Report of harm possibly related to (68)Ga-DOTATATE was rare (6 of 974), and no study reported major toxicity or safety issues.
CONCLUSION
No direct comparison of octreotide and (68)Ga-DOTATATE imaging for diagnosis and staging in an unbiased population of NETs has been published. Available information in the peer-reviewed literature regarding diagnostic efficacy and safety supports the use of (68)Ga-DOTATATE for imaging of NETs where it is available.
Topics: Humans; Intestinal Neoplasms; Lung Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Pentetic Acid; Positron Emission Tomography Computed Tomography; Stomach Neoplasms
PubMed: 26769864
DOI: 10.2967/jnumed.115.165803 -
World Journal of Gastroenterology Feb 2015To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo... (Review)
Review
AIM
To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors (NETs).
METHODS
We searched PubMed and Cochrane Library from 1998-2012, 5 conferences (American Society of Clinical Oncology, Endocrine Society, European Neuroendocrine Tumor Society, European Society for Medical Oncology, North American Neuroendocrine Tumor Society) from 2000-2013 using MeSH and keyterms including neuroendocrine tumors, carcinoid tumor, carcinoma, neuroendocrine, and octreotide. Bibliographies of accepted articles were also searched. Two reviewers reviewed titles, abstracts, and full-length articles. Studies that reported data on efficacy and safety of ≥ 30 mg/mo octreotide-LAR for NETs in human subjects, published in any language were included in the review.
RESULTS
The search identified 1086 publications, of which 238 underwent full-text review (20 were translated into English); 17 were included in the review. Studies varied in designs, subjects, octreotide-LAR regimens, and definition of outcomes. Eleven studies reported use of higher doses to control symptoms and tumor progression, although symptom severity and formal quality-of-life analysis were not quantitatively measured. Ten studies reported efficacy, describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo. Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression. Eight studies reported safety; there was no evidence of increased toxicity associated with doses of octreotide-LAR > 30 mg/mo.
CONCLUSION
As reported in this review, octreotide-LAR at doses > 30 mg/mo is being prescribed for symptom and tumor control in NET patients. Furthermore, expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.
Topics: Antineoplastic Agents, Hormonal; Gastrointestinal Neoplasms; Humans; Neuroendocrine Tumors; Octreotide; Treatment Outcome
PubMed: 25684964
DOI: 10.3748/wjg.v21.i6.1945 -
Pharmacoepidemiology and Drug Safety Jan 2017Octreotide is a synthetic peptide analog of naturally occurring somatostatin. Octreotide is used off-label in children <6 years of age for hyperinsulinism,...
BACKGROUND
Octreotide is a synthetic peptide analog of naturally occurring somatostatin. Octreotide is used off-label in children <6 years of age for hyperinsulinism, chylothorax, and gastrointestinal bleeding. There is a lack of controlled data on efficacy or potential adverse events from this off-label use.
METHODS
Three pediatric hospitals participated in this study. Patients were hospitalized January 2007-December 2010 and administered octreotide for congenital hyperinsulinism (CHI) at least 1 day. Variables assessed included octreotide dosage, patient demographics, medical interventions, concomitant medicines, serious adverse events (SAEs) including necrotizing enterocolitis (NEC), and mortality.
RESULTS
The 103 patient sample had a median gestational age of 38 weeks. During the study period, two patients died: one from NEC and the other from cardiomyopathy/sepsis. There were 11 other SAEs in the 101 surviving patients.
CONCLUSION
This study highlights potential risks in administering octreotide off-label. This study, like several other published studies, has highlighted NEC in a full-term infant treated with octreotide. It is important to study the efficacy and the safety of octreotide for hyperinsulinism. In the interim, it might be prudent to prescribe octreotide in CHI neonates only in the absence of other risk factors for NEC. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Child; Child, Preschool; Enterocolitis, Necrotizing; Female; Gastrointestinal Agents; Humans; Hyperinsulinism; Infant; Infant, Newborn; Male; Octreotide; Off-Label Use; Retrospective Studies; Risk Factors
PubMed: 27910218
DOI: 10.1002/pds.4144 -
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 -
Acta Cirurgica Brasileira 2022To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model.
PURPOSE
To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model.
METHODS
Rats were subjected to midline incision followed by TBI in the prefrontal cortex region. After 72 hours, the behavioural and neurological deficits tests were performed, which included memory testing on Morris water maze for 5 days. Octreotide (15 and 30 mg/kg i.p.) was administered 30 minutes before subjecting to TBI, and its administration was continued for three days.
RESULTS
In TBI-subjected rats, administration of octreotide restored on day 4 escape latency time (ELT) and increased the time spent in the target quadrant (TSTQ) on day 5, suggesting the improvement in learning and memory. It also increased the expression of H2S, Nrf2, and cystathionine-γ-lyase (CSE) in the prefrontal cortex, without any significant effect on cystathionine-β-synthase. Octreotide also decreased the TNF-α levels and neurological severity score. However, co-administration of CSE inhibitor (D,L-propargylglycine) abolished octreotide-mediated neurofunctional recovery, decreased the levels of H2S and Nrf2 and increased the levels of TNF-α.
CONCLUSIONS
Octreotide improved the neurological functions in TBI-subjected rats, which may be due to up-regulation of H2S biosynthetic enzyme (CSE), levels of H2S and Nrf2 and down-regulation of neuroinflammation.
Topics: Animals; Brain Injuries, Traumatic; Hydrogen Sulfide; NF-E2-Related Factor 2; Octreotide; Rats; Tumor Necrosis Factor-alpha
PubMed: 35239813
DOI: 10.1590/ACB361204 -
The Oncologist Jul 2021Octreotide acetate (octreotide) is the most prescribed and most studied somatostatin congener, or analog, for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and... (Review)
Review
Octreotide acetate (octreotide) is the most prescribed and most studied somatostatin congener, or analog, for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and carcinoid syndrome, the latter of which may be characterized by debilitating diarrhea and flushing. Approved in the U.S. more than 30 years ago, octreotide is widely used to control the symptoms of carcinoid syndrome and has been shown to demonstrate antiproliferative activity. The two formulations available in the U.S. include a subcutaneous immediate-release (IR) injection introduced in 1989 and a long-acting repeatable (LAR) intramuscular injection approved in 1999. Lanreotide depot (lanreotide), a more recent somatostatin congener, has been available in the U.S. since 2014. Despite widespread use of octreotide LAR, several key challenges exist with the current depot-based treatment paradigm. Studies indicate that LAR formulations are associated with continued unmet patient needs, owing in part to a loss of bioactivity over time that may necessitate progressive supplemental treatment with IR octreotide to adequately control symptoms. Clinicians should understand the key differences in the pharmacokinetic profiles of the LAR and IR formulations that may contribute to bioactivity loss and somatostatin receptor desensitization. In addition, there is a need to re-evaluate the role of IR octreotide in combination with depot therapy to provide consistent bioavailability and better control of carcinoid syndrome symptoms. The purpose of this review is to explore all these issues and to re-establish a rationale for the IR formulation, particularly with respect to novel use cases and its use during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: There is a need to re-evaluate the role of immediate-release octreotide in combination with depot therapy to provide consistent bioavailability and better control of carcinoid syndrome symptoms.
Topics: COVID-19; Humans; Neuroendocrine Tumors; Octreotide; Pandemics; SARS-CoV-2; Somatostatin
PubMed: 34097784
DOI: 10.1002/onco.13847 -
Current Medical Research and Opinion Dec 2009Acromegaly is characterized by overproduction of growth hormone (GH) by the pituitary gland. GH stimulates the synthesis of insulin-like growth factor-I (IGF-I), and the... (Review)
Review
BACKGROUND
Acromegaly is characterized by overproduction of growth hormone (GH) by the pituitary gland. GH stimulates the synthesis of insulin-like growth factor-I (IGF-I), and the somatic growth and metabolic dysfunction that characterize acromegaly are a consequence of elevated GH and IGF-I levels. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, slow-growing neoplasms that have usually metastasized by the time of diagnosis. The majority of GEP-NETs are carcinoid tumors whose syndrome is caused by the hypersecretion of biogenic amines, peptides and polypeptides responsible for the principal symptoms of diarrhea and flushing.
METHODS
The MEDLINE and EMBASE databases were searched for preclinical and clinical studies of octreotide (Sandostatin* ), a potent synthetic somatostatin analogue, in patients with acromegaly or GEP-NETs.
OBJECTIVE
This article reviews the 20 years of clinical experience with octreotide and the impact it has made in patients with acromegaly or GEP-NETs.
RESULTS
Octreotide has proven to be an essential component in the management strategy of acromegaly and GEP-NETs over the past 20 years. The multiple beneficial effects of octreotide throughout the body, combined with its established safety profile (the most common adverse effects are injection-site pain and gastrointestinal events), have made it an appealing option for clinicians. The advent of the long-acting release (LAR) formulation of octreotide provided additional benefits to patients through monthly administration, while maintaining the efficacy and tolerability profile of the daily subcutaneous formulation.
CONCLUSIONS
Octreotide is a potent synthetic somatostatin analogue that has become the mainstay of medical therapy for tumor control in neuroendocrine disorders such as acromegaly and GEP-NETs. The development of octreotide LAR offered a further advancement; less frequent dosing provided valuable benefits in quality of life to patients, with equivalent efficacy and tolerability. Moreover, recent results from the PROMID study have confirmed the antiproliferative effect of octreotide LAR in patients with well-differentiated metastatic GEP-NETs of the midgut. New therapeutic uses of octreotide are currently under investigation in a variety of clinical settings.
Topics: Acromegaly; Animals; Clinical Trials as Topic; Delayed-Action Preparations; Drug Design; Drug Evaluation, Preclinical; Humans; Octreotide; Retrospective Studies; Somatostatin
PubMed: 19842996
DOI: 10.1185/03007990903328959 -
Nuclear Medicine Review. Central &... 2016Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005,... (Review)
Review
Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005, 99mTc-EDDA/HYNIC-Tyr3-Octreotide has been used in clinical imaging and achieved high impact in management of patients with neuroendocrine tumors. Knowing the limitations and pitfalls is essential to provide ac-curate diagnosis. Therefore, the potential pitfalls associated with the use of 99mTc-EDDA/HYNIC-TOC are reviewed on the basis of own experience. Data were analyzed of 310 patients who underwent somatostatin receptor scintigraphy with 99mTc-Tektrotyd. Pitfalls during radiolabeling process or acquisition can worsen the sensitivity of SRS (somatostatin receptor scintigraphy). Recognizing physi-ological and clinical pitfalls, the diagnostic accuracy will improve.
Topics: Edetic Acid; Humans; Octreotide; Organotechnetium Compounds; Radionuclide Imaging; Sensitivity and Specificity
PubMed: 27479887
DOI: 10.5603/NMR.2016.0019 -
Journal of Medical Toxicology :... Jun 2010The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published... (Review)
Review
The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published from 1965 to 2008 using combinations of the terms octreotide, antidote, sulfonylurea, overdose, poisoning, and toxicity was performed. References from identified articles were reviewed for additional sources. Animal studies, case reports, case series, and randomized controlled trials were evaluated. An animal model of sulfonylurea overdose demonstrates that octreotide reduces the number of refractory sulfonylurea-induced hypoglycemic episodes. Published case reports describe the use of octreotide to prevent recurrent hypoglycemia after sulfonylurea overdose. A retrospective case series demonstrates that administration of octreotide decreases the need for supplemental dextrose boluses as well as hypoglycemic events. Two prospective, controlled trials determined that octreotide and supplemental dextrose increase blood glucose concentrations with fewer hypoglycemic events. Based on animal and human data, there is sufficient evidence to recommend the use of octreotide with supplemental dextrose for the treatment of sulfonylurea-induced hypoglycemia.
Topics: Animals; Diazoxide; Diuretics; Gastrointestinal Agents; Glucagon; Humans; Hypoglycemia; Hypoglycemic Agents; Octreotide; Sulfonylurea Compounds
PubMed: 20352540
DOI: 10.1007/s13181-010-0064-z -
Journal of Nuclear Medicine : Official... Sep 2017Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be... (Meta-Analysis)
Meta-Analysis Review
Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, for In-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate than In-octreotide. Although Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.
Topics: Diagnostic Imaging; Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Sensitivity and Specificity
PubMed: 28280220
DOI: 10.2967/jnumed.117.191197