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Siraj ES, Lieb DC, Tesfaye S, Pacak K. Editorial on Special Issue in Memory of Aaron I. Vinik: From Autonomic Diabetic Neuropathy to Neuroendocrine Tumors. Endocr Pract 2025; 31:1-3. [PMID: 39447697 DOI: 10.1016/j.eprac.2024.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Affiliation(s)
- Elias S Siraj
- Division of Endocrine and Metabolic Disorders, Department of Internal Medicine, Eastern Virginia Medical School at Old Dominion University; Norfolk, Virginia
| | - David C Lieb
- Division of Endocrine and Metabolic Disorders, Department of Internal Medicine, Eastern Virginia Medical School at Old Dominion University; Norfolk, Virginia.
| | - Solomon Tesfaye
- Academic Directorate of Diabetes & Endocrinology, Sheffield Teaching Hospitals and the University of Sheffield, Royal Hallamshire Hospital; Sheffield, United Kingdom
| | - Karel Pacak
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Clinical Research Center; Bethesda, Maryland
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Oda K, Murata T, Tsujimoto K, Tanaka F, Takahashi D, Saiki R, Hirabayashi Y, Tsunoda A, Saito K, Yuasa H, Imai H, Katayama K, Dohi K. A case of carcinoid syndrome probably exacerbated by hemodialysis in which prochlorperazine maleate was effective. CEN Case Rep 2024; 13:135-140. [PMID: 37606883 PMCID: PMC10982206 DOI: 10.1007/s13730-023-00814-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 07/31/2023] [Indexed: 08/23/2023] Open
Abstract
Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy.
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Affiliation(s)
- Keiko Oda
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Tomohiro Murata
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
| | - Kayo Tsujimoto
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Fumika Tanaka
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Daisuke Takahashi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Ryosuke Saiki
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Yosuke Hirabayashi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Akira Tsunoda
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kanako Saito
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Hiroto Yuasa
- Department of Pathology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Hiroshi Imai
- Department of Pathology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kan Katayama
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Kaoru Dohi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
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Ruggeri RM, Benevento E, De Cicco F, Fazzalari B, Guadagno E, Hasballa I, Tarsitano MG, Isidori AM, Colao A, Faggiano A. Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies. J Endocrinol Invest 2023; 46:213-234. [PMID: 36038743 DOI: 10.1007/s40618-022-01905-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 08/16/2022] [Indexed: 01/25/2023]
Abstract
PURPOSE Neuroendocrine neoplasms can occur as part of inherited disorders, usually in the form of well-differentiated, slow-growing tumors (NET). The main predisposing syndromes include: multiple endocrine neoplasias type 1 (MEN1), associated with a large spectrum of gastroenteropancreatic and thoracic NETs, and type 4 (MEN4), associated with a wide tumour spectrum similar to that of MEN1; von Hippel-Lindau syndrome (VHL), tuberous sclerosis (TSC), and neurofibromatosis 1 (NF-1), associated with pancreatic NETs. In the present review, we propose a reappraisal of the genetic basis and clinical features of gastroenteropancreatic and thoracic NETs in the setting of inherited syndromes with a special focus on molecularly targeted therapies for these lesions. METHODS Literature search was systematically performed through online databases, including MEDLINE (via PubMed), and Scopus using multiple keywords' combinations up to June 2022. RESULTS Somatostatin analogues (SSAs) remain the mainstay of systemic treatment for NETs, and radiolabelled SSAs can be used for peptide-receptor radionuclide therapy for somatostatin receptor (SSTR)-positive NETs. Apart of these SSTR-targeted therapies, other targeted agents have been approved for NETs: the mTOR inhibitor everolimus for lung, gastroenteropatic and unknown origin NET, and sunitinib, an antiangiogenic tyrosine kinase inhibitor, for pancreatic NET. Novel targeted therapies with other antiangiogenic agents and immunotherapies have been also under evaluation. CONCLUSIONS Major advances in the understanding of genetic and epigenetic mechanisms of NET development in the context of inherited endocrine disorders have led to the recognition of molecular targetable alterations, providing a rationale for the implementation of treatments and development of novel targeted therapies.
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Affiliation(s)
- R M Ruggeri
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "Gaetano Martino" University Hospital, 98125, Messina, Italy.
| | - E Benevento
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy
| | - F De Cicco
- SSD Endocrine Disease and Diabetology, ASL TO3, Pinerolo, TO, Italy
| | - B Fazzalari
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - E Guadagno
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy
| | - I Hasballa
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - M G Tarsitano
- Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - A M Isidori
- Gruppo NETTARE, Policlinico Umberto I, Università Sapienza, Rome, Italy
| | - A Colao
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy
- UNESCO Chair "Education for Health and Sustainable Development", Federico II University, Naples, Italy
| | - A Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
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Lim JY, Pommier RF. Clinical Features, Management, and Molecular Characteristics of Familial Small Bowel Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2021; 12:622693. [PMID: 33732215 PMCID: PMC7959745 DOI: 10.3389/fendo.2021.622693] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 01/21/2021] [Indexed: 12/14/2022] Open
Abstract
Small bowel neuroendocrine tumors are rare tumors with an increasing incidence over the last several decades. Early detection remains challenging because patients commonly develop symptoms late in the disease course, often after the tumors have metastasized. Although these tumors were thought to arise from sporadic genetic mutations, large epidemiological studies strongly support genetic predisposition and increased risk of disease in affected families. Recent studies of familial small bowel neuroendocrine tumors have identified several novel genetic mutations. Screening for familial small bowel neuroendocrine tumors can lead to earlier diagnosis and improved patient outcomes. This review aims to summarize the current knowledge of molecular changes seen in familial small bowel neuroendocrine tumors, identify clinical features specific to familial disease, and provide strategies for screening and treatment.
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Eads JR, Reidy-Lagunes D, Soares HP, Chan JA, Anthony LB, Halfdanarson TR, Naraev BG, Wolin EM, Halperin DM, Li D, Pommier RF, Zacks JS, Morse MA, Metz DC. Differential Diagnosis of Diarrhea in Patients With Neuroendocrine Tumors. Pancreas 2020; 49:1123-1130. [PMID: 32991344 DOI: 10.1097/mpa.0000000000001658] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience diarrhea that can have a debilitating effect on quality of life. Diarrhea also may develop in response to other hormonal syndromes associated with NETs, surgical complications, medical comorbidities, medications, or food sensitivities. Limited guidance on the practical approach to the differential diagnosis of diarrhea in these patients can lead to delays in appropriate treatment. This clinical review and commentary underscore the complexity in identifying the etiology of diarrhea in patients with NETs. Based on our collective experience and expertise, we offer a practical algorithm to guide medical oncologists and other care providers to expedite effective management of diarrhea and related symptoms in patients with NETs.
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Affiliation(s)
- Jennifer R Eads
- From the Department of Medicine, Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Diane Reidy-Lagunes
- Department of Medicine, Division of Solid Tumor, Gastrointestinal Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Heloisa P Soares
- Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
| | - Lowell B Anthony
- Division of Medical Oncology, University of Kentucky Medical Center, Markey Cancer Center, Lexington, KY
| | | | - Boris G Naraev
- Division of Cancer Medicine, Banner MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center, Gilbert, AZ
| | - Edward M Wolin
- Department of Medicine, Division of Hematology/Oncology, Icahn School of Medicine, Center for Carcinoid and Neuroendocrine Tumors, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Daneng Li
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA
| | - Rodney F Pommier
- Division of Surgical Oncology, Oregon Health & Science University, Portland, OR
| | - Jerome S Zacks
- Department of Medicine (Cardiology), The Mount Sinai School of Medicine, The Carcinoid Heart Center, New York, NY
| | - Michael A Morse
- Department of Medical Oncology, Duke University Medical Center, Durham, NC
| | - David C Metz
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Khan MS, Walter T, Buchanan-Hughes A, Worthington E, Keeber L, Feuilly M, Grande E. Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review. World J Gastroenterol 2020; 26:4537-4556. [PMID: 32874063 PMCID: PMC7438200 DOI: 10.3748/wjg.v26.i30.4537] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 05/22/2020] [Accepted: 06/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Approximately 20% of patients with neuroendocrine tumours (NETs) develop carcinoid syndrome (CS), characterised by flushing and diarrhoea. Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion. Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs (GEP-NETs), other causes to consider include pancreatic enzyme insufficiency (PEI), bile acid malabsorption and small intestinal bacterial overgrowth. If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea, these treatments may be ineffective against the diarrhoea, risking detrimental effects to patient quality of life.
AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.
METHODS Electronic databases (MEDLINE, Embase and the Cochrane Library) were searched from inception to September 12, 2018 using terms for NETs and diarrhoea. Congresses, systematic literature review bibliographies and included articles were also hand-searched. Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported. Studies were screened by two independent reviewers at abstract and full-text stages. Framework synthesis was adapted to synthesise quantitative and qualitative data. The definition of qualitative data was expanded to include all textual data in any section of relevant publications.
RESULTS Forty-seven publications (44 studies) were included, comprising a variety of publication types, including observational studies, reviews, guidelines, case reports, interventional studies, and opinion pieces. Most reported on PEI on/after treatment with somatostatin analogs; 9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI. Where reported, 14.3%–50.7% of patients received pancreatic enzyme replacement therapy. Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption (80%), small intestinal bacterial overgrowth (23.6%-62%), colitis (20%) and infection (7.1%). Diagnostic approaches included faecal elastase, breath tests, tauroselcholic (selenium-75) acid (SeHCAT) scan and stool culture, although evidence on the effectiveness or diagnostic accuracy of these approaches was limited. Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation. From the identified evidence, if diarrhoea is assumed to be CS diarrhoea, consequences include uncontrolled diarrhoea, malnutrition, and perceived ineffectiveness of CS treatment. Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team, including gastroenterologists.
CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use. This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches, to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.
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Affiliation(s)
- Mohid S Khan
- Department of Gastroenterology and Neuroendocrine Tumours, University Hospital of Wales, Cardiff CF14 4XW, United Kingdom
| | - Thomas Walter
- Department d'Oncologie Médicale, Hospices Civils de Lyon, Lyon 69003, France
| | | | - Emma Worthington
- Evidence Development, Costello Medical, Cambridge CB1 2JH, United Kingdom
| | - Lucie Keeber
- Medical Affairs, Ipsen, Slough SL1 3XE, United Kingdom
| | - Marion Feuilly
- Health Economics and Outcomes Research, Ipsen, Boulogne-Billancourt 92100, France
| | - Enrique Grande
- Oncology Department, MD Anderson Cancer Center, Madrid 28033, Spain
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Anthony LB, Kulke MH, Caplin ME, Bergsland E, Öberg K, Pavel M, Hörsch D, Warner RRP, O'Dorisio TM, Dillon JS, Lapuerta P, Kassler-Taub K, Jiang W. Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome. Oncologist 2019; 24:e662-e670. [PMID: 30651397 PMCID: PMC6693702 DOI: 10.1634/theoncologist.2018-0236] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 11/20/2018] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome. SUBJECTS, MATERIALS, AND METHODS Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated. RESULTS Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4. CONCLUSION Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. IMPLICATIONS FOR PRACTICE Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.
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Affiliation(s)
- Lowell B Anthony
- Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA
| | - Matthew H Kulke
- Boston University Medical Center, Boston, Massachusetts, USA
| | - Martyn E Caplin
- Neuroendocrine Tumor Unit, ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom
| | - Emily Bergsland
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Kjell Öberg
- Department of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Marianne Pavel
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin, Berlin, Germany
| | - Dieter Hörsch
- Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Richard R P Warner
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York New York, USA
| | - Thomas M O'Dorisio
- Department of Internal Medicine - Endocrinology and Metabolism, University of Iowa, Iowa City, Iowa, USA
| | - Joseph S Dillon
- Department of Internal Medicine - Endocrinology and Metabolism, University of Iowa, Iowa City, Iowa, USA
| | - Pablo Lapuerta
- Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA
| | | | - Wenjun Jiang
- Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA
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Abstract
Neuroendocrine tumors, including carcinoids, are rare and insidiously growing tumors. Related to their site of origin, tumors can be functional, causing various forms of the carcinoid syndrome, owing to the overproduction of serotonin, histamine, or other bioactive substances. They often invade adjacent structures or metastasize to the liver and elsewhere. Treatment includes multimodal approaches, including cytoreductive surgery, locoregional embolization, cytotoxic therapy, peptide receptor radionuclide therapy, and various targeted therapies with goals of symptom relief and control of tumor growth. This article summarizes current and emerging approaches to management and reviews several promising future therapies.
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Affiliation(s)
- Paul Benjamin Loughrey
- Department of Ophthalmology, Royal Victoria Hospital, Belfast Trust, Grosvenor Road, Belfast, BT12 6BA, UK; Department of Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Trust, Grosvenor Road, Belfast, BT12 6BA, UK
| | - Dongyun Zhang
- Department of Medicine, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA
| | - Anthony P Heaney
- Department of Medicine, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA; Department of Neurosurgery, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA.
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de Celis Ferrari ACR, Glasberg J, Riechelmann RP. Carcinoid syndrome: update on the pathophysiology and treatment. Clinics (Sao Paulo) 2018; 73:e490s. [PMID: 30133565 PMCID: PMC6096975 DOI: 10.6061/clinics/2018/e490s] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 03/02/2018] [Indexed: 12/15/2022] Open
Abstract
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.
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Affiliation(s)
| | - João Glasberg
- Disciplina de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Rachel P Riechelmann
- Disciplina de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
- Departamento de Oncologia, AC Camargo Cancer Center Sao Paulo, SP, BR
- *Corresponding author. E-mail:
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Burton T, Lapuerta P. Economic analysis of inadequate symptom control in carcinoid syndrome in the United States. Future Oncol 2018; 14:2361-2370. [PMID: 30095284 DOI: 10.2217/fon-2018-0129] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
AIM We investigated the healthcare resource utilization and costs of patients with dose escalations beyond recommended levels of long-acting octreotide for persistent carcinoid syndrome (CS) symptoms. MATERIALS & METHODS A retrospective study of US health insurance claims included 358 adults with ≥1 medical claim for CS and ≥6 claims for long-acting octreotide (10-30 mg) between 1 July 2006 and 31 December 2013. RESULTS Pre-escalation per-patient per-month outcomes and costs were lower versus post-escalation, including vascular conditions (0.11 vs 0.21), metastasis/secondary neoplasms (0.45 vs 0.74), total all-cause costs (US$4116 vs US$8305; p < 0.001) and CS-related costs (US$3156 vs US$7101; p < 0.001). CONCLUSION Higher mean pre-escalation per-patient per-month resource use and costs post-escalation primarily attributable to CS-related ambulatory care suggests continuing challenges in managing CS despite octreotide dose escalation.
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Affiliation(s)
- Tanya Burton
- Optum Life Sciences, Health Economics and Outcomes Research, Boston, MA 02215, USA
| | - Pablo Lapuerta
- Lexicon Pharmaceuticals, Inc., The Woodlands, TX 77381, USA
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11
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Mirakhur B, Pavel ME, Pommier RF, Fisher GA, Phan AT, Massien C, Liyanage N, Lowenthal SP, Vinik AI. BIOCHEMICAL RESPONSES IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS WITH NEUROENDOCRINE TUMORS: POOLED ANALYSIS OF 2 PHASE 3 TRIALS. Endocr Pract 2018; 24:S1530-891X(20)35469-0. [PMID: 30084687 DOI: 10.4158/ep-2018-0296] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
OBJECTIVE Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes. METHODS Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly. RESULTS Of 319 pooled patients, 86% and 95% had baseline 5-HIAA and CgA data, respectively, with 47% and 74% having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a decrease in biomarker levels at week 12, with statistical significance reached in the CgA cohort (not reached vs. 14.4 months; P<.0001). A large proportion (87%) of patients without symptoms of CS in the CLARINET study had detectable levels of 5-HIAA (48% >ULN). In ELECT, patients with CS who received lanreotide and experienced a biochemical response (≥50% decrease from baseline) achieved greater symptom control. CONCLUSION This pooled analysis of two randomized, placebo-controlled trials demonstrated that 5-HIAA and CgA are secreted as biochemical biomarkers in many patients with NETs, regardless of clinical syndromes. Significant biochemical response was associated with improved clinical outcomes, as measured by improved PFS or improved CS symptom control. ABBREVIATIONS 5-HIAA = 5-hydroxyindoleacetic acid; CgA = chromogranin A; CI = confidence interval; CLARINET = Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors; CS = carcinoid syndrome; ELECT = Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment; HR = hazard ratio; ITT = intention-to-treat; NET = neuroendocrine tumor; PanNET = pancreatic NET; PFS = progression-free survival; PPI = proton pump inhibitor; SSA = somatostatin analogue; ULN = upper limit of normal.
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Rastogi V, Singh D, Mazza JJ, Parajuli D, Yale SH. Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila. Clin Med Res 2018; 16:16-28. [PMID: 29650525 PMCID: PMC6108509 DOI: 10.3121/cmr.2017.1379a] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 11/30/2017] [Accepted: 12/21/2017] [Indexed: 02/08/2023]
Abstract
Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.
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Affiliation(s)
- Vaibhav Rastogi
- University of Central Florida College of Medicine/HCA Consortium Graduate Medical Education, North Florida Regional Medical Center, 6500 W Newberry Rd, Gainesville, FL 32605
- University of Central Florida College of Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827
| | - Devina Singh
- Feinstein Institute for Medical Research, 350 Community Dr. Manhasset, NY 11030
| | - Joseph J Mazza
- Marshfield Clinic Research Institute, 1000 North Oak Avenue, Marshfield, WI 54449
| | - Dipendra Parajuli
- University of Louisville, Department of Medicine, Gastroenterology, Hepatology and Nutrition. Director, Fellowship Training Program, Director, Medical Procedure Unit Louisville VAMC 401 East Chestnut Street, Louisville, KY 40202
| | - Steven H Yale
- University of Central Florida College of Medicine/HCA Consortium Graduate Medical Education, North Florida Regional Medical Center, 6500 W Newberry Rd, Gainesville, FL 32605.
- University of Central Florida College of Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827
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Sinnamon AJ, Neuwirth MG, Vining CC, Sharoky CE, Yang YX, Kelz RR, Fraker DL, Roses RE, Karakousis GC. Prophylactic Cholecystectomy at Time of Surgery for Small Bowel Neuroendocrine Tumor Does Not Increase Postoperative Morbidity. Ann Surg Oncol 2017; 25:239-245. [PMID: 29067602 DOI: 10.1245/s10434-017-6093-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Prophylactic cholecystectomy at time of surgery for small bowel neuroendocrine tumor (SBNET) has been advocated, as these patients often go on to require somatostatin analogue therapy, which is known to increase risk of cholestasis and associated complications. Little is known regarding patterns of adoption of this practice or its associated morbidity. METHODS The American College of Surgeons National Surgical Quality Improvement Program database (2008-2014) was queried to identify patients who underwent SBNET resection. The risk differences of morbidity and mortality associated with performance of concurrent cholecystectomy were determined with multivariable adjustment for confounders. RESULTS Among 1300 patients who underwent SBNET resection, 144 (11.1%) underwent concurrent cholecystectomy. Median age of patients undergoing cholecystectomy was 62 years [interquartile range (IQR) 52-69 years], and 75 were male. They more commonly had disseminated cancer (36.1 vs. 11.6%, p < 0.001) or SBNET located in duodenum (10.4 vs. 4.9%, p = 0.045) without difference in other baseline characteristics. Operative time was significantly longer in the cholecystectomy group (median 172 vs. 123 min, p < 0.001). Rate of postoperative morbidity was not significantly different between cholecystectomy and no-cholecystectomy groups (11.8 vs. 11.1%, p = 0.79). After adjustment for confounding, the risk difference of morbidity attributable to cholecystectomy was + 0.4% [95% confidence interval (CI) - 4.9 to + 5.6%]. Mortality within 30 days was not significantly different between cholecystectomy and no-cholecystectomy groups (1.4 vs. 0.6%, p = 0.29). CONCLUSIONS Concurrent cholecystectomy at time of resection of SBNET is not associated with higher morbidity or mortality yet is performed in a minority of patients. Prospective study can identify which patients may derive benefit from this approach.
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Affiliation(s)
- Andrew J Sinnamon
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. .,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
| | - Madalyn G Neuwirth
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Charles C Vining
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Catherine E Sharoky
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Yu-Xiao Yang
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA
| | - Rachel R Kelz
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Douglas L Fraker
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Robert E Roses
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Giorgos C Karakousis
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
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Fisher GA, Wolin EM, Liyanage N, Pitman Lowenthal S, Mirakhur B, Pommier RF, Shaheen M, Vinik A. Patient-Reported Symptom Control of Diarrhea and Flushing in Patients with Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a Randomized, Placebo-Controlled, Double-Blind and 32-Week Open-Label Study. Oncologist 2017; 23:16-24. [PMID: 29038234 DOI: 10.1634/theoncologist.2017-0284] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 09/06/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND In the double-blind (DB) ELECT study, lanreotide depot/autogel significantly reduced versus placebo the need for short-acting octreotide for symptomatic carcinoid syndrome (CS) control in neuroendocrine tumor (NET) patients. Here we present patient-reported symptom data during DB and initial open-label (IOL) treatment. MATERIALS AND METHODS Adults with NETs and CS history, with/without prior somatostatin analog use, were randomized to 16 weeks' DB lanreotide 120 mg subcutaneous or placebo every 4 weeks, followed by 32 weeks' IOL lanreotide. Patients recorded diarrhea and/or flushing frequency and severity daily by Interactive Voice (Web) Response System for 1 month prior to randomization and throughout the study. RESULTS Of 115 patients randomized (n = 59 lanreotide, n = 56 placebo), 56 lanreotide and 45 placebo patients enrolled in the IOL phase. During DB treatment, least square (LS) mean percentages of days with moderate/severe diarrhea and/or flushing were significantly lower for lanreotide (23.4%) versus placebo (35.8%; LS mean difference [95% confidence interval]: -12.4 [-20.73 to -4.07]; p = .004). For DB lanreotide patients, average daily composite (frequency × severity) diarrhea scores improved significantly between DB and IOL treatment (mean difference: -0.71 [-1.20 to -0.22]; p = .005), and remained stable for diarrhea and/or flushing. For DB placebo patients, composite scores for diarrhea, flushing, and diarrhea and/or flushing improved significantly between DB and IOL treatment (mean differences: -1.07 [-1.65 to -0.49]; -1.06 [-1.93 to -0.19]; and -2.13 [-3.35 to -0.91]; all p ≤ .018). CONCLUSION Improved diarrhea and flushing control in CS patients during 16-week lanreotide treatment was sustained during maintenance of lanreotide treatment for the 32-week IOL phase (48 weeks total). IMPLICATIONS FOR PRACTICE This study prospectively collected daily patient-reported data on diarrhea and flushing from the ELECT trial to evaluate the direct impact of lanreotide depot on patients' relief of carcinoid syndrome symptoms. Treatment with lanreotide depot was associated with significant reductions in the percentages of days patients reported symptoms of diarrhea and flushing, as well as reductions in the frequency and severity of daily symptoms compared with placebo during 16 weeks of double-blind treatment. These improvements were sustained for 32 additional weeks of open-label lanreotide treatment (i.e., through week 48 of treatment), resulting in clinically meaningful, long-term symptom reduction.
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Affiliation(s)
- George A Fisher
- Stanford University School of Medicine, Stanford, California, USA
| | - Edward M Wolin
- Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
| | | | | | - Beloo Mirakhur
- Ipsen Biopharmaceuticals, Basking Ridge, New Jersey, USA
| | | | - Montaser Shaheen
- University of New Mexico Cancer Center, Albuquerque, New Mexico, USA
| | - Aaron Vinik
- Eastern Virginia Medical School, Norfolk, Virginia, USA
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Hassan SA, Banchs J, Iliescu C, Dasari A, Lopez-Mattei J, Yusuf SW. Carcinoid heart disease. Heart 2017; 103:1488-1495. [DOI: 10.1136/heartjnl-2017-311261] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 04/18/2017] [Accepted: 04/20/2017] [Indexed: 12/28/2022] Open
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Lamarca A, Barriuso J, McNamara MG, Hubner RA, Valle JW. Telotristat ethyl: a new option for the management of carcinoid syndrome. Expert Opin Pharmacother 2016; 17:2487-2498. [PMID: 27817224 DOI: 10.1080/14656566.2016.1254191] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Many patients with neuroendocrine tumour-related carcinoid syndrome treated with somatostatin analogues (SSA) won't achieve adequate symptom relief with the SSA alone; new treatment options are required. Telotristat ethyl is a tryptophan hydroxylase inhibitor, developed for the treatment of carcinoid syndrome. Areas covered: This review summarises the evidence supporting the role of telotristat ethyl in the management of carcinoid syndrome. Rationale, pharmacodynamics, pharmacokinetics, metabolism, clinical experience, efficacy and toxicity profiles are covered. Expert opinion: The efficacy of telotristat ethyl in producing a statistically-significant and clinically-meaningful reduction in daily bowel movements has been confirmed in phase III clinical trials. Two pivotal trials, TELESTAR and TELECAST, explored the role of telotristat ethyl in the management of patients with carcinoid syndrome refractory to SSAs focusing on patients with ≥4 and <4 daily bowel movements, respectively. In addition, benefit was confirmed in patient-reported outcomes. Based on activity and safe toxicity profile, telotristat ethyl is pending regulatory agencies evaluation and is likely to add to the armamentarium used to treat carcinoid syndrome. Long-term safety and efficacy data will be available from the ongoing TELEPATH study. The impact on carcinoid heart disease, mesenteric fibrosis and other long-term complications of carcinoid syndrome as well as its role earlier in patients' pathways remain investigational.
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Affiliation(s)
- Angela Lamarca
- a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK
| | - Jorge Barriuso
- a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.,b Faculty of Medical, Biological and Human Sciences , University of Manchester , Manchester , UK
| | - Mairéad G McNamara
- a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.,c Institute of Cancer Sciences , University of Manchester , Manchester , UK
| | - Richard A Hubner
- a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK
| | - Juan W Valle
- a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.,c Institute of Cancer Sciences , University of Manchester , Manchester , UK
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Abstract
Cutaneous flushing is a common presenting complaint in endocrine disorders. The pathophysiology of flushing involves changes in cutaneous blood flow triggered by multiple intrinsic factors that are either related to physiology or disease. Flushing can be divided into episodic or persistent causes. Episodic flushing is mediated by the release of endogenous vasoactive mediators or medications, while persistent flushing results in a fixed facial erythema with telangiectasia and cyanosis due to slow-flowing deoxygenated blood in large cutaneous blood vessels. The differential diagnosis of cutaneous flushing in neuroendocrine disorders is limited, yet encompasses a broad spectrum of benign and malignant entities, including carcinoid syndrome, pheochromocytoma, Cushing syndrome, medullary thyroid cancer, and pancreatic neuroendocrine tumors. In this review, we provide a concise and up-to-date discussion on the differential diagnosis and approach of flushing in neuroendocrinology.
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Affiliation(s)
- Fady Hannah-Shmouni
- Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
| | - Constantine A Stratakis
- Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA
| | - Christian A Koch
- Division of Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.
- G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, USA.
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Dalal A, Stone M. Intraoperative Management of Carcinoid Heart Disease for Valvular Surgery. J Cardiothorac Vasc Anesth 2016; 30:1046-9. [DOI: 10.1053/j.jvca.2015.10.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Indexed: 11/11/2022]
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Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA. EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. Endocr Pract 2016; 22:1068-80. [PMID: 27214300 DOI: 10.4158/ep151172.or] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVE To evaluate the efficacy and safety of lanreotide depot/autogel 120 mg for the control of carcinoid syndrome (CS) symptoms in patients with neuroendocrine tumors (NETs). METHODS This was a 16-week, randomized, double-blind, phase 3 trial (Clinicaltrials.gov: NCT00774930). Patients with/without prior somatostatin analog (SSA) use were randomized to lanreotide depot/autogel 120 mg or placebo every 4 weeks, with access to short-acting octreotide as rescue medication. The primary endpoint was the percentage of days in which short-acting octreotide was used, which was assessed from daily diaries using an analysis of covariance including the stratification variables baseline short-acting octreotide use and frequency of diarrhea/flushing. The proportions of patients experiencing treatment success was a supportive analysis. Adverse events were recorded at all visits. RESULTS A total of 115 patients were enrolled (lanreotide, n = 59; placebo, n = 56). The adjusted mean (95% confidence interval [CI]) percentage of days with rescue octreotide use (primary endpoint) was significantly lower in the lanreotide (33.7%; 95% CI, 25.0%-42.4%) versus the placebo group (48.5%; 95% CI, 39.6%-57.4%), representing an absolute difference of -14.8% (95% CI, -26.8% to -2.8%; P = .017). The odds ratio of full/partial treatment success (≤3 days short-acting octreotide use weeks 12 to 15) was significantly greater with lanreotide than placebo (2.4; 95% CI, 1.1-5.3; P = .036). No new safety concerns were identified, and lanreotide was well tolerated. CONCLUSION Lanreotide depot/autogel is effective for the control of CS symptoms in patients (SSA-naïve or experienced) with NETs. ABBREVIATIONS AE = adverse event BMI = body mass index CS = carcinoid syndrome ELECT = Evaluating Lanreotide Efficacy and safety as a Carcinoid-syndrome Treatment HRQoL = health-related quality of life LTOLE = long-term open-label extension NET = neuroendocrine tumor OL = open label SSA = somatostatin analog.
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