Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome

The oncologist

article

Lowell B. Anthony¹  Joseph S. Dillon²  Pablo Lapuerta³  Kenneth Kassler-Taub³  Wenjun Jiang³  Matthew H. Kulke⁴  Martyn E. Caplin⁵  Emily Bergsland⁶  Kjell Öberg⁷  Marianne Pavel⁸  Dieter Hörsch⁹  Richard R.P. Warner^1,10  Thomas M. O'Dorisio² 

[1] Markey Cancer Center, University of Kentucky;Department of Internal Medicine – Endocrinology and Metabolism, University of Iowa;Inc.;Boston University Medical Center;Neuroendocrine Tumor Unit, ENETS Centre of Excellence, Royal Free Hospital, United Kingdom;Department of Medicine, University of California;Department of Endocrine Oncology, Uppsala University;Department of Hepatology and Gastroenterology, Charité – Universitätsmedizin;Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors;Division of Gastroenterology, Icahn School of Medicine at Mount Sinai

关键词: Malignant carcinoid syndrome;    Tryptophan hydroxylase;    Telotristat ethyl;    Serotonin;    Diarrhea;    Neuroendocrine tumors;   

DOI  :  10.1634/theoncologist.2018-0236

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background 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. Subjects, Materials, and Methods 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. Results 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. Conclusion Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. Implications for Practice Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.

【 授权许可】

CC BY|CC BY-NC