Martyn Caplin

Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial.

CONTEXTnCarcinoid syndrome (CS) is associated with elevated serotonin, diarrhea, flushing, and increased risk of valvular heart disease. Many patients respond to somatostatin analogs initially, but response diminishes in most patients. Additional options are needed.nnnOBJECTIVEnTo assess whether telotristat etiprate (TE) can reduce gastrointestinal symptoms in CS and reduce urinary 5-hydroxyindoleacetic acid (u5-HIAA; a biomarker of serotonin).nnnDESIGNnA prospective, exploratory, dose-escalating 12-week, open-label, multicenter study of TE with efficacy and safety analyses.nnnSETTINGnA multicenter study.nnnPATIENTSnEligible patients had metastatic, well-differentiated, neuroendocrine tumors and CS with ≥ four bowel movements (BMs) per day. Somatostatin analog use was allowed.nnnINTERVENTIONSnTE, a novel oral inhibitor of peripheral serotonin synthesis.nnnMAIN OUTCOME MEASURESnPrimary: safety. Secondary: daily BMs, stool form, and u5-HIAA.nnnRESULTSnFifteen patients were enrolled, and 14 completed the treatment period. All patients experienced reductions in BMs per day (mean decrease, 43.5%). A 74.2% mean reduction in u5-HIAA, the main metabolite of serotonin, was observed, with generally greater reductions in patients with greater reductions in BMs per day. Nine patients (75%) reported adequate relief of gastrointestinal symptoms at 12 weeks, compared with two (17%) at baseline. Stool form and flushing also improved. Adverse events were mostly gastrointestinal (n = 10; 67%), consistent with underlying illness; three adverse events were serious (abdominal pain, diarrhea, and gastroenteritis) but were judged unrelated.nnnCONCLUSIONnTE was generally safe and well tolerated. Patients experienced substantial improvement in CS and reductions in u5-HIAA, consistent with the mechanism of action of TE. These results support further evaluation in phase 3 studies.

Weight change associated with telotristat ethyl in the treatment of carcinoid syndrome

1University Hospitals Coventry and Warwickshire NHS Trust; 2Zentralklinik Bad Berka; 3Lexicon Pharmaceuticals, Inc.; 4Charité–Universitätsmedizin; 5Friedrich-Alexander-Universität; 6University of Manchester/The Christie NHS Foundation Trust; 7Royal Free Hospital; 8UCSF Helen Diller Family Comprehensive Cancer Center; 9Stanford University; 10University of Kentucky; 11Hospital Universitario Ramón y Cajal; 12Uppsala University; 13Icahn School of Medicine at Mount Sinai; 14Hôpital Edouard Herriot, Hospices Civils de Lyon; 15Dana-Farber Cancer Institute