{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:24:44Z","timestamp":1790717084630,"version":"4.1.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were \u20130.81 for telotristat ethyl 250 mg ( P &lt; .001) and \u20120.69 for telotristat ethyl 500 mg ( P &lt; .001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were \u20130.9, \u20131.7, and \u20132.1, respectively. Responses, predefined as a BM frequency reduction \u2265 30% from baseline for \u2265 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 ( P &lt; .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2016.69.2780","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T13:26:36Z","timestamp":1487856396000},"page":"14-23","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":265,"title":["Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome"],"prefix":"10.1200","volume":"35","author":[{"given":"Matthew H.","family":"Kulke","sequence":"first","affiliation":[{"name":"Matthew H. Kulke, Dana-Farber Cancer Institute, Boston; Douglas Fleming, Ipsen Bioscience, Cambridge, MA; Dieter H\u00f6rsch, Zentralklinik Bad Berka, Bad Berka; Marianne Pavel, Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany; Martyn E. Caplin, Royal Free Hospital, London; Juan W. Valle, The University of Manchester-The Christie National Health Service Foundation Trust, Manchester, United Kingdom; Lowell B. Anthony, University of Kentucky, Lexington, KY; Emily Bergsland, University of California at San Francisco..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"H\u00f6rsch","sequence":"additional","affiliation":[{"name":"Matthew H. Kulke, Dana-Farber Cancer Institute, Boston; Douglas Fleming, Ipsen Bioscience, Cambridge, MA; Dieter H\u00f6rsch, Zentralklinik Bad Berka, Bad Berka; Marianne Pavel, Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany; Martyn E. Caplin, Royal Free Hospital, London; Juan W. Valle, The University of Manchester-The Christie National Health Service Foundation Trust, Manchester, United Kingdom; Lowell B. Anthony, University of Kentucky, Lexington, KY; Emily Bergsland, University of California at San Francisco..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyn E.","family":"Caplin","sequence":"additional","affiliation":[{"name":"Matthew H. Kulke, Dana-Farber Cancer Institute, Boston; Douglas Fleming, Ipsen Bioscience, Cambridge, MA; Dieter H\u00f6rsch, Zentralklinik Bad Berka, Bad Berka; Marianne Pavel, Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany; Martyn E. Caplin, Royal Free Hospital, London; Juan W. Valle, The University of Manchester-The Christie National Health Service Foundation Trust, Manchester, United Kingdom; Lowell B. 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