Somatostatin Analogs in Clinical Practice: a Review.
Ontology highlight
ABSTRACT:
SUBMITTER: Gomes-Porras M
PROVIDER: S-EPMC7084228 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Somatostatin Analogs in Clinical Practice: a Review.
Gomes-Porras Mariana M Cárdenas-Salas Jersy J Álvarez-Escolá Cristina C
International journal of molecular sciences 20200229 5
Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, ...[more]
Similar Datasets
Project description:Somatostatin receptors (SSTRs) are variably expressed by a variety of malignancies. Using radiolabeled somatostatin analogs (SSAs), the presence of SSTRs on tumor cells may be exploited for molecular imaging and for peptide receptor radionuclide therapy. 111In-DTPA-octreotide has long been the standard in SSTR scintigraphy. A major leap forward was the introduction of gallium-68 labeled SSAs for positron emission tomography (PET) offering improved sensitivity. Tracers currently in clinical use are 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC), 68Ga-DOTA-Tyr3-octreotate (68Ga-DOTATATE) and 68Ga-DOTA-1-NaI3-octreotide (68Ga-DOTANOC), collectively referred to as 68Ga-DOTA-peptides. 68Ga-DOTA-peptide PET has superseded 111In-DTPA-octreotide scintigraphy as the modality of choice for SSTR imaging. However, implementation of 68Ga-DOTA-peptides in routine clinical practice is often limited by practical, economical and regulatory factors related to the use of the current generation of 68Ge/68Ga generators. Centralized production and distribution is challenging due to the low production yield and relatively short half-life of gallium-68. Furthermore, gallium-68 has a relatively long positron range, compromising spatial resolution on modern PET cameras. Therefore, possibilities of using other PET radionuclides are being explored. On the other hand, new developments in SSTR PET ligands are strongly driven by the need for improved lesion targeting, especially for tumors with low SSTR expression. This may be achieved by using peptide vectors having a higher affinity for the SSTR or a broader affinity profile for the different receptor subtypes or by using compounds recognizing more binding sites, such as SSTR antagonists. This review gives an overview of recent developments leading to the next generation of clinical PET tracers for SSTR imaging.
| S-EPMC6261874 | biostudies-literature
Project description:For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs.A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts. Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20-0.59; p = .000072).In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs.
| S-EPMC3380872 | biostudies-literature
Project description:BackgroundThe use of somatostatin analogues (SSAs) has not been formally approved in pulmonary neuroendocrine tumours (NETs) in the absence of positive controlled trials, even though it is recommended as a potential therapeutic option in recent guidelines.Patients and methodsWe have assessed the use of SSA in the general practice in Austria by retrospectively analysing patients with pulmonary NETs referred to our European Neuroendocrine Tumor Society centre in Vienna for second opinion or further therapy. In addition, we have analysed the somatostatin receptor (SSTR) expression of those patients by immunohistochemistry (IHC) and SSTR imaging, e.g. 68Ga-DOTANOC-positron emission tomography/computed tomography, and whether such analyses had been carried out before referral at our centre.ResultsOut of 34 patients (19 atypical and 15 typical carcinoids) with metastatic or advanced disease, 10/34 (29%) had been prescribed SSA before referral. No IHC for SSTR had been carried out, and only 9/34 (27%) had undergone SSTR imaging by nuclear medicine. Sufficient material for IHC was available in 29/34 (85%) patients and SSTR-IHC was rated negative in 13/29 (45%), weakly positive in 4/29 (14%), moderately positive in 5/29 (17%) and strongly positive in 7/29 (24%) patients. On SSTR imaging, 8/34 patients (24%) were positive, 13/34 (38%) negative and 13/34 patients (38%) showed a mix of positive and negative NET lesions. In 11/29 (38%) patients with both IHC and imaging available, discordance of SSTR expression on imaging and histological assessment was detected.ConclusionsThese data show that uncritical use of SSA should be discouraged, and assessment of SSTR, preferably by imaging, is mandatory before prescription of SSA in pulmonary NETs.
| S-EPMC9271480 | biostudies-literature
Project description:Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand-receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.
| S-EPMC7504749 | biostudies-literature
Project description:A meta-analysis has systematically investigated the antineoplastic efficacy and safety of somatostatin analogs (SSAs) in advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Randomized controlled trials (RCTs) reporting the hazard ratio (HR) for disease progression (DP) were evaluated. Response rate and risk ratio (RR) for adverse events were also analyzed. A total of 289 patients (143 receiving SSAs vs. 146 placebo) were evaluated from two RCTs. A significant benefit from SSAs in terms of disease control was observed (HR 0.41, 95% CI: 0.29 to 0.58, P < 0.01; I20%), response rate being 58.0% vs. 32.2%, respectively.The occurrence of adverse events significantly differed from the placebo arm only in terms of biliary stones (RR 3.79, 95% CI: 1.28 to 11.17, P = 0.02; I20%). In conclusion, SSAs showed an antiproliferative effect in advanced GEP-NETs, with a good safety profile.
| S-EPMC5542298 | biostudies-literature
Project description:We previously detected and investigated nine altered microRNAs in small intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease. The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be also detected in patient serum samples, 2) investigate a potential somatostatin analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples and 3) elucidate whether the serum microRNA levels in samples collected in different hospitals are predictable and steady. Our results show that tissue microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a and -200a levels are lower in SI-NET untreated patients than in SSA-treated patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215 levels do not show any difference in untreated SI-NET patients and SSA-treated patients at all different stages. Our findings also show that miR-200a exhibits an atypical behavior with high levels in both untreated and SSA-treated patients at liver metastasis stage, and unequivocally never at the earlier stages. Serum samples collected in two hospitals keep alike microRNA level pattern, elucidating that the results are not dependent on samples handling. In conclusion, SI-NET tissue microRNAs are always detectable in untreated and SSA-treated patient serum samples, SSAs play an unknown role in eliciting SSA-treated patients' microRNA levels higher than in untreated patients, and this study enlightens that miR-200a might be involved in the liver metastasis during SI-NET progression.
| S-EPMC4420277 | biostudies-other
Project description:BACKGROUND:Neuroendocrine tumors (NETs) are neoplasms arising most often in the GI tract, pancreas, or lung. Diagnosis of NETs is often delayed until the disease is advanced, because of the variable and nonspecific nature of the initial symptoms. Surgical resection for cure is therefore not an option for most patients. METHODS:Somatostatin analogues represent the cornerstone of therapy for patients with NETs. This article reviews the important role that somatostatin analogues continue to play in the treatment of patients with NETs. RESULTS:Octreotide was the first somatostatin analogue to be developed; more than 30 years of data have accumulated demonstrating its efficacy and safety. Lanreotide is another somatostatin analogue in clinical use, and pasireotide is a promising somatostatin analogue in development. Newer long-acting depot formulations are now available offering once-monthly administration. Although octreotide was initially developed for symptom control, recent results indicate that it also has an antiproliferative effect, significantly increasing time to progression in patients with midgut NETs. Combinations of octreotide with other targeted therapies may further improve patient outcomes. Findings in recent studies of the combination of octreotide and the mTOR inhibitor everolimus are encouraging. The combinations of octreotide with other agents (eg, interferon-?, bevacizumab, cetuximab, AMG-706, and sunitinib) are being investigated. CONCLUSIONS:Somatostatin analogues have been used to treat the symptoms of NETs for decades and also have an antineoplastic effect, markedly prolonging progression-free survival. Somatostatin analogues are likely to remain the cornerstone of treatment for most patients with advanced NETs. Promising new combination therapies are undergoing clinical investigation.
| S-EPMC3481148 | biostudies-literature
Project description:Peptide receptor radionuclide therapy (PRRT) has been shown to be an effective treatment for neuroendocrine tumors (NETs) if curative surgery is not an option. A majority of NETs abundantly express somatostatin receptors. Consequently, following administration of somatostatin (SST) analogs labeled with γ-emitting radionuclides, these tumors can be imaged for diagnosis, staging or follow-up purposes. Furthermore, when β-emitting radionuclides are used, radiolabeled peptides (radiopeptides) can also be used for the treatment for NET patients. Even though excellent results have been achieved with PRRT, complete responses are still rare, which means that there is room for improvement. In this review, we highlight some of the directions currently under investigation in pilot clinical studies or in preclinical development to achieve this goal. Although randomized clinical trials are still lacking, early studies have shown that tumor response might be improved by application of other radionuclides, such as α-emitters or radionuclide combinations, or by adjustment of radiopeptide administration routes. Individualized dosimetry and better insight into tumor and normal organ radiation doses may allow adjustment of the amount of administered activity per cycle or the number of treatment cycles, resulting in more personalized treatment schedules. Other options include the application of novel (radiolabeled) SST analogs with improved tumor uptake and radionuclide retention time, or a combination of PRRT with other systemic therapies, such as chemotherapy or treatment with radio sensitizers. Though promising directions appear to bring improvements of PRRT within reach, additional research (including randomized clinical trials) is needed to achieve such improvements.
| S-EPMC3991004 | biostudies-literature
Project description:BackgroundLong-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited.Materials and methodsTo assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints.ResultsA total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea.ConclusionSSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%.Implications for practiceThe results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
| S-EPMC8018333 | biostudies-literature
Project description:IntroductionSomatostatin analogs (SSAs) are used to treat neuroendocrine tumors (NETs) and acromegaly. Two first-generation SSAs, octreotide long-acting release (OCT LAR) and lanreotide autogel/depot (LAN), are available. A systematic literature review (SLR) was conducted to investigate which characteristics beyond efficacy are most important in patient and healthcare practitioner (HCP) experience of LAN and OCT when used to treat acromegaly and NETs.MethodsMEDLINE, Embase, the Cochrane Library, and Database of Abstracts of Reviews of Effect were searched from database inception to January 2019 with terms for first-generation SSAs, NETs, acromegaly, preferences, decision-making, and human factors. Key congresses in 2016-2018 and SLR bibliographies were hand-searched. Two independent reviewers screened articles at title/abstract and full-text stage. Publications fulfilling pre-specified inclusion criteria reported patient or HCP perspectives of LAN or OCT, or any factors affecting treatment perspectives for NETs or acromegaly.ResultsA total of 1110 unique records were screened, of which 21 studies were included, reporting from the perspectives of patients (n = 18) and/or HCPs (n = 9). Perspectives were collected using shared decision-making frameworks, questionnaires, informal patient opinion, and a Delphi panel. Where patient preference was specifically reported, LAN was preferred in 4/5 studies and OCT LAR in 1/5. Common factors underlying treatment experience included technical problems with injections and associated pain, emotional quality/anxiety of injections, time and convenience of treatment administration, and independence. Immediate aspects of injections appeared most important to patients, though the possibilities of extended dosing intervals and self-/partner-injection with LAN were also notable factors.ConclusionsStudy outcomes favored LAN in this SLR, with factors surrounding injection administration most influential in treatment experience. The findings of this SLR provide a basis that could inform development of decision-making criteria, with patient and HCP treatment perspectives considered. Future studies should utilize a common method to report preference and associated drivers.
| S-EPMC7799425 | biostudies-literature