{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:30:50Z","timestamp":1772580650136,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Subjects, Materials, and Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0236","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T20:45:59Z","timestamp":1547671559000},"page":"e662-e670","source":"Crossref","is-referenced-by-count":10,"title":["Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome"],"prefix":"10.1093","volume":"24","author":[{"given":"Lowell B.","family":"Anthony","sequence":"first","affiliation":[{"name":"Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew H.","family":"Kulke","sequence":"additional","affiliation":[{"name":"Boston University Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martyn E.","family":"Caplin","sequence":"additional","affiliation":[{"name":"Neuroendocrine Tumor Unit, ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Bergsland","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjell","family":"\u00d6berg","sequence":"additional","affiliation":[{"name":"Department of Endocrine Oncology, Uppsala University, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Pavel","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dieter","family":"H\u00f6rsch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Endocrinology, Center for Neuroendocrine Tumors, Zentralklinik Bad Berka, Bad Berka, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard R.P.","family":"Warner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"O'Dorisio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine \u2013 Endocrinology and Metabolism, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph S.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine \u2013 Endocrinology and Metabolism, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Lapuerta","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Kassler-Taub","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"2021122507443368400_R1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol"},{"key":"2021122507443368400_R2","volume-title":"2015. 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