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Πέμπτη 19 Οκτωβρίου 2017

Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea

Abstract

Introduction

Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed.

Methods

This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome.

Discussion

Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I–III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients.

Future directions

The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.



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