The Use of Telotristat Ethyl for the Treatment of Carcinoid Syndrome

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Telotristat ethyl, a tryptophan hydroxylase inhibitor, may be beneficial for patients with carcinoid syndrome.
Telotristat ethyl, a tryptophan hydroxylase inhibitor, may be beneficial for patients with carcinoid syndrome.

Telotristat ethyl, a tryptophan hydroxylase inhibitor, may be beneficial for patients with carcinoid syndrome, which is characterized by diarrhea, flushing, bronchial constriction, and possible progression to heart failure, and which can develop as a result of increased serotonin levels in advanced neuroendocrine tumors (NETs).1

First-line therapy for carcinoid syndrome is somatostatin analogs (SSAs); these are, however, associated with disease recurrence. The objective of this study was to analyze the efficacy and safety of telotristat ethyl in patients with carcinoid syndrome who progressed on first-line SSA therapy.

In this phase 3 clinical trial, researchers analyzed 135 patients who had metastatic NETs, carcinoid syndrome, and at least 4 bowel movements (BMs) a day. Efficacy endpoints included mean reductions in BMs, abdominal pain severity, flushing episodes, SSA use, and change in urinary 5-HIAA (u5-HIAA)–a serotonin marker–from baseline.

The researchers state that telotristat ethyl shows increased efficacy over placebo, as seen in the reduced frequency of BMs from baseline to week 12. There was a higher percentage of responders in the telotristat ethyl group compared to the placebo group (40% vs 20%).

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Telotristat ethyl was also associated with decreased u5-HIAA levels; it is therefore a feasible treatment option for patients who progressed on first-line treatments such as SSAs.

Adverse effects were similar between treatment groups.                           

Reference

  1. Kulke MH, Horsch D, Caplin ME, et al. Telotristat ethyl, a tryptophan hydroxylase inhibitor for the treatment of carcinoid syndrome. J Clin Oncol. 2016 Oct 28. doi: 10.1200/JCO.2016.69.2780 [Epub ahead of print] 

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