{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:19:05Z","timestamp":1792293545577,"version":"4.4.0"},"reference-count":92,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This review reports on the currently available medical treatment options for the control of symptoms due to carcinoid syndrome in patients with neuroendocrine tumors. The efficacy and adverse events (AEs) of approved drugs such as somatostatin analogues (SSA), telotristat ethyl (TE) and interferon\u2010alpha, are reviewed. Somatostatin analogues remain the standard treatment of carcinoid syndrome based on the high expression of somatostatin receptors and the resulting inhibition of secretion of bioactive compounds; their use is associated with relatively mild AEs, involving mainly the gastrointestinal system, and being usually transient. Although dose escalation of SSA remains an unapproved option, it is clinically implemented to alleviate symptoms in refractory carcinoid syndrome and supported by the most recent guidelines. The side effects associated with the increased dose are in general mild and consistent with standard dose of SSA. Telotristat ethyl, an oral inhibitor of tryptophan hydroxylase, the rate\u2010limiting enzyme in serotonin biosynthesis, represents a rather novel innovative treatment option in patients with carcinoid syndrome suffering from diarrhea and complements the standard therapy of SSA. Given the low toxicity profile, TE may be considered an early add\u2010on treatment to SSA in patients with uncontrolled carcinoid syndrome. However, further prolonged follow\u2010up of patients treated with TE may be needed to exclude potential AEs, such as liver toxicity or depressed mood, in patients with long\u2013term treatment. Interferon alpha is a cytokine with direct inhibitory effect on hormone secretion and tumor cell proliferation and an approved therapy in carcinoid syndrome but is associated with significant AEs in the majority of the patients requiring frequently dose reduction. The finding of a more favorable tolerability of pegylated interferon needs to be confirmed in a prospective study.<\/jats:p>","DOI":"10.1111\/jne.13174","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T09:49:40Z","timestamp":1654681780000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy, safety and unmet needs of evolving medical treatments for carcinoid syndrome"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4159-2511","authenticated-orcid":false,"given":"Anna","family":"Koumarianou","sequence":"first","affiliation":[{"name":"Hematology\u2010Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-8912","authenticated-orcid":false,"given":"Kosmas","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health \u00d6rebro University  \u00d6rebro Sweden"},{"name":"2nd Department of Surgery \u201cKorgialenio\u2010Benakio\u201d, Red Cross General Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Tsoli","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Department of Internal Medicine National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Department of Internal Medicine National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Pavel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Universitatsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-16-0200"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)64173-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9061777"},{"key":"e_1_2_8_5_1","article-title":"Managing carcinoid heart disease in patients with neuroendocrine tumors","author":"Koffas A","year":"2020","journal-title":"Ann Endocrinol (Paris)"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443171"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-198207000-00008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0000000000001215"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30110-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol13020006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa924"},{"issue":"2","key":"e_1_2_8_12_1","article-title":"The role of serum 5\u2010HIAA as a predictor of progression and an alternative to 24\u2010h urine 5\u2010HIAA in well\u2010differentiated neuroendocrine neoplasms","volume":"10","author":"Wedin M","year":"2021","journal-title":"Biology (Basel)"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000225948"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.03.304"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198312153092406"},{"issue":"5","key":"e_1_2_8_16_1","first-page":"505","article-title":"The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide","volume":"65","author":"Kvols LK","year":"1992","journal-title":"Yale J Biol Med"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(82)90087-X"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/02841869309083912"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198609113151102"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.2.600"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(87)90073-7"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.2.279"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP151172.OR"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S84177"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04174.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.8510"},{"key":"e_1_2_8_27_1","unstructured":"Neuroendocrinology 104 1 Placebo\u2010controlled double\u2010blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID):results of long\u2010term survival"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04083.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61742-X"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607427"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2019.11.003"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740330903379525"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000471880"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2010.510130"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-018-3734-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000082875"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04693.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2015.12.013"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316158"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.388"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-11-913_1"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000215)88:4<770::AID-CNCR6>3.0.CO;2-0"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758834016675803"},{"issue":"3","key":"e_1_2_8_44_1","first-page":"81","article-title":"Above\u2010label doses of octreotide\u2010LAR in patients with metastatic small intestinal carcinoid tumors","volume":"6","author":"Strosberg J","year":"2013","journal-title":"Gastrointest Cancer Res"},{"issue":"1","key":"e_1_2_8_45_1","first-page":"190","article-title":"Safety and efficacy of high doses Lanreotide treatment in patients with progressive neuroendocrine tumors: results from a prospective phase II trial. Meeting abstract 1929. 14th annual ENETS conference for the diagnosis and treatment of neuroendocrine tumor disease. Barcelona, Spain","volume":"105","author":"Albertelli M","year":"2017","journal-title":"Neuroendocrinology"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.1375"},{"issue":"2","key":"e_1_2_8_47_1","first-page":"231","article-title":"Antitumor effects of interferon","volume":"516","author":"Gresser I","year":"1978","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1159\/000080748"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198307213090301"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1989.7.7.865"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08125.x"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19931115)72:10<3099::AID-CNCR2820721035>3.0.CO;2-4"},{"issue":"11","key":"e_1_2_8_53_1","first-page":"1297","article-title":"Treatment of malignant carcinoid tumors with human leukocyte interferon: long\u2010term results","volume":"70","author":"Oberg K","year":"1986","journal-title":"Cancer Treat Rep"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3109\/02841869309083918"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-200405000-00022"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.3109\/02841869309083916"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(05)00481-7"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.12.142"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2006.26.8"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.4072"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-09-0104"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.4155\/cli.15.10"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-14-0173"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2247"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.2780"},{"key":"e_1_2_8_66_1","unstructured":"PavelM GrossD BenaventM et al.Efficacy and safety results of telotristat ethyl in patients with carcinoid syndrome during the double\u2010blind treatment period of the TELECAST phase 3 clinical trial. NANETS; 30th Sept\u20101st Oct 2016 2016; Jackson Wyoming."},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1159\/000516958"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-020-00375-2"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S261257"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0921"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-015-0233-2"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq670"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0367"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx078"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.8574"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0224"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-014-0585-6"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00186"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.1992.tb00050.x"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(98)00009-4"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.05.003"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335597"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2014.08.009"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab289"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5459-x"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000013390"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-016-3189-z"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i47.6857"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1159\/000511482"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2018.03.010"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30633"},{"key":"e_1_2_8_92_1","first-page":"2","article-title":"role of diet in the management of carcinoid syndrome: clinical recommendations for nutrition in patients with neuroendocrine tumors","volume":"1","author":"Artale S","year":"2020","journal-title":"Nutr Cancer"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12955-016-0527-2"}],"updated-by":[{"DOI":"10.1111\/jne.13361","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000}}],"container-title":["Journal of Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.13174","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jne.13174","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.13174","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T01:26:02Z","timestamp":1692840362000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jne.13174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":92,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/jne.13174"],"URL":"https:\/\/doi.org\/10.1111\/jne.13174","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNE.13174\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13174\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13174\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13174\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13174\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13174\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13174\/v1\/review2","asserted-by":"object"}]},"ISSN":["0953-8194","1365-2826"],"issn-type":[{"value":"0953-8194","type":"print"},{"value":"1365-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"2022-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13174"}}