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J Clin Oncol. 2017 Jan;35(1):14-23. Epub 2016 Oct 28.

Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome.

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Matthew H. Kulke, Dana-Farber Cancer Institute, Boston; Douglas Fleming, Ipsen Bioscience, Cambridge, MA; Dieter Hörsch, Zentralklinik Bad Berka, Bad Berka; Marianne Pavel, Charité-Universitätsmedizin, 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 Helen Diller Family Comprehensive Cancer Center, San Francisco; Pamela L. Kunz, Stanford University, Palo Alto, CA; Kjell Öberg and Staffan Welin, Uppsala University, Uppsala, Sweden; Richard R.P. Warner, Icahn School of Medicine at Mount Sinai, New York, NY; Catherine Lombard-Bohas, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Pablo Lapuerta, Phillip Banks, Shanna Jackson, Brian Zambrowicz, and Arthur T. Sands, Lexicon Pharmaceuticals, The Woodlands, TX; and Enrique Grande, Hospital Universitario Ramón y Cajal, Madrid, Spain.


Purpose 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. Patients and Methods 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. Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg ( P < .001) and ‒0.69 for telotristat ethyl 500 mg ( P < .001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were -0.9, -1.7, and -2.1, respectively. Responses, predefined as a BM frequency reduction ≥ 30% from baseline for ≥ 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 < .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. Conclusion 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.

[Indexed for MEDLINE]

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