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Pituitary Feb 2021Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize... (Review)
Review
Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize outcomes. Given significant novel recent advances in understanding acromegaly natural history and individualized therapies, the Pituitary Society invited acromegaly experts to critically review the current literature in the context of Endocrine Society guidelines and Acromegaly Consensus Group statements. This update focuses on how recent key advances affect treatment decision-making and outcomes, and also highlights the likely role of recently FDA-approved therapies as well as novel combination therapies within the treatment armamentarium.
Topics: Acromegaly; Animals; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Octreotide; Pituitary Neoplasms; Receptors, Somatostatin
PubMed: 33079318
DOI: 10.1007/s11102-020-01091-7 -
The Journal of Clinical Endocrinology... Jan 2022Currently, the first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve... (Review)
Review
Currently, the first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot, and nasal octreotide, may improve patients' adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788, and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.
Topics: Acromegaly; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Growth Hormone-Secreting Pituitary Adenoma; Humans; Octreotide; Peptides, Cyclic; Precision Medicine; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Somatostatin; Somatostatin; Treatment Outcome
PubMed: 34618894
DOI: 10.1210/clinem/dgab726 -
International Journal of Molecular... Jan 2021Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin's role as a neurotransmitter in the central... (Review)
Review
Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin's role as a neurotransmitter in the central nervous system and a motility mediator in the gastrointestinal tract has been well defined, and its function in tumorigenesis in various cancers (gliomas, carcinoids, and carcinomas) is being studied. Many studies have shown a potential stimulatory effect of serotonin on cancer cell proliferation, invasion, dissemination, and tumor angiogenesis. Although the underlying mechanism is complex, it is proposed that serotonin levels in the tumor and its interaction with specific receptor subtypes are associated with disease progression. This review article describes serotonin's role in cancer pathogenesis and the utility of the serotonin pathway as a potential therapeutic target in cancer treatment. Octreotide, an inhibitor of serotonin release, is used in well-differentiated neuroendocrine cancers, and the tryptophan hydroxylase (TPH) inhibitor, telotristat, is currently being investigated in clinical trials to treat patients with metastatic neuroendocrine tumors and advanced cholangiocarcinoma. Several in vitro studies have shown the anticancer effect of 5-HT receptor antagonists in various cancers such as prostate cancer, breast cancer, urinary bladder, colorectal cancer, carcinoid, and small-cell lung cancer. More in vivo studies are needed to assess serotonin's role in cancer and its potential use as an anticancer therapeutic target. Serotonin is also being evaluated for its immunoregulatory properties, and studies have shown its potential anti-inflammatory effect. Therefore, it would be of interest to explore the combination of serotonin antagonists with immunotherapy in the future.
Topics: Antineoplastic Agents, Hormonal; Carcinoma, Neuroendocrine; Cell Movement; Cell Proliferation; Cholangiocarcinoma; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Neovascularization, Pathologic; Octreotide; Phenylalanine; Pyrimidines; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Signal Transduction; Tryptophan Hydroxylase; Tumor Cells, Cultured
PubMed: 33525332
DOI: 10.3390/ijms22031268 -
Respiratory Medicine Oct 2019A chylothorax, also known as chylous pleural effusion, is an uncommon cause of pleural effusion with a wide differential diagnosis characterized by the accumulation of... (Review)
Review
A chylothorax, also known as chylous pleural effusion, is an uncommon cause of pleural effusion with a wide differential diagnosis characterized by the accumulation of bacteriostatic chyle in the pleural space. The pleural fluid will have either or both triglycerides >110 mg/dL and the presence of chylomicrons. It may be encountered following a surgical intervention, usually in the chest, or underlying disease process. Management of a chylothorax requires a multidisciplinary approach employing medical therapy and possibly surgical intervention for post-operative patients and patients who have failed medical therapy. In this review, we aim to discuss the anatomy, fluid characteristics, etiology, and approach to the diagnosis of a chylothorax.
Topics: Antineoplastic Agents, Hormonal; Chylothorax; Diagnosis, Differential; Exudates and Transudates; Humans; Lymphography; Lymphoscintigraphy; Octreotide; Pleural Effusion; Postoperative Period; Radiography, Thoracic; Suction; Thoracentesis; Thoracic Duct; Tomography, X-Ray Computed; Triglycerides
PubMed: 31454675
DOI: 10.1016/j.rmed.2019.08.014 -
Frontiers in Endocrinology 2022Lu-177 has been developed for the treatment of patients with peptide receptor radionuclide therapy (PRRT). A second generation pure no-carrier-added Lu-177 has a high... (Review)
Review
Lu-177 has been developed for the treatment of patients with peptide receptor radionuclide therapy (PRRT). A second generation pure no-carrier-added Lu-177 has a high specific activity and has waste disposal advantages over the first generation carrier-added Lu-177. PRRT has recently been developed for the treatment of neuroendocrine tumors (NETs). The majority of pancreatic and gastroenteric NETs (GEP-NETs) express the somatostatin receptors (SSTRs) 2 and 5. These receptors can be specifically targeted with a somatostatin peptide analogue (DOTATOC/DOTATATE) which can be chelated to a positron emission tomography (PET) emitting radioisotope such as Ga-68 for imaging or to a β-emitting radioisotope Lu-177 for therapy. A key advantage of this approach is that the receptor expression can be demonstrated by PET imaging before the patient is treated. Clinical studies in G1 and G2 GEP-NETS have demonstrated that PRRT is extremely effective in terms of progression free survival (PFS), symptom control and quality of life, with a well-established safety profile. A beneficial effect on outcome survival awaits to be confirmed. The first commercially available product Lu-177-DOTATATE was approved following the NETTER-1 trial in G1 and G2 GE-NETS. Lu-177-DOTATATE 7,4 GBq every 8 weeks for 4 cycles, together with octreotide LAR 30 mg monthly, demonstrated a median PFS of 28,4 months compared to 8,5 months for octreotide LAR 60 mg monthly. A second pivotal study COMPETE is currently in progress, comparing no carrier-added (n.c.a.) Lu-177-DOTATOC to the m-TOR inhibitor Everolimus in both GE-NETs and PNETs. Two studies, NETTER-2 and COMPOSE are currently underway in patients with high grade G2 and G3 NETs. Novel SSTR antagonists are being developed as next generation targeting molecules for SSTR2-expressing tumors. Antagonists have a higher tumor binding to receptors than agonists, opening up the potential indications for SSTR2 targeting to tumors which have a relatively lower expression of SSTR2 compared to NET such as small cell lung cancer, hepatocellular carcinoma and breast cancer. In addition to Lu-177, radioisotopes with different radiation properties such as Tb-161 and the α-emitter Ac-225 are being developed which have the potential to improve treatment efficacy across the range of G1 to G3 NETs.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Gallium Radioisotopes; Actinium; Quality of Life; Radioisotopes; Radiopharmaceuticals
PubMed: 36387893
DOI: 10.3389/fendo.2022.941832 -
Clinical Cancer Research : An Official... Jun 2021Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic... (Review)
Review
Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-I-MIBG therapy was approved by the FDA and both Lu-DOTATATE and I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Humans; Iodine Radioisotopes; Lutetium; Octreotide; Organometallic Compounds; Paraganglioma; Pheochromocytoma; Positron Emission Tomography Computed Tomography; Radioisotopes; Radiopharmaceuticals; Radiotherapy
PubMed: 33685867
DOI: 10.1158/1078-0432.CCR-20-3703 -
Expert Review of Gastroenterology &... Nov 2019: Lutetium-[DOTA°,Tyr]octreotate (Lu-DOTATATE) is a type of peptide receptor radionuclide therapy that garnered FDA approval in January 2018 for the treatment of... (Review)
Review
: Lutetium-[DOTA°,Tyr]octreotate (Lu-DOTATATE) is a type of peptide receptor radionuclide therapy that garnered FDA approval in January 2018 for the treatment of somatostatin receptor-positive gastroenteropancreatic (GEP) neuroendocrine tumor (NET) patients. The therapy approval was based on findings from the randomized international phase III NETTER-1 trial as well as outcome data from a large European registry. The mechanism of the drug stems directly from its structure: a somatostatin analog (octreotate) selectively binding to somatostatin receptor expressing cells and being internalized, along with a chelated beta-emitting isotope Lu.: Herein we describe the pharmacology, clinical efficacy and adverse event data from prospective and retrospective studies with Lu-DOTATATE. We discuss the role of Lu-DOTATATE within the current treatment landscape for GEP NET patients.: Lu-DOTATATE represents a unique addition to the treatment armamentarium for GEP NETs because of its potential to elicit tumor cytoreduction, which is rare among other existing treatment options, and prolonged disease control. Where Lu-DOTATATE fits into the treatment sequence for GEP NET patients remains an area of active investigation.
Topics: Animals; Gastrointestinal Neoplasms; Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiopharmaceuticals; Treatment Outcome
PubMed: 31652074
DOI: 10.1080/17474124.2019.1685381