Telotristat Ethyl for Patients With Carcinoid Syndrome Associated With Chest Pain and Hypertension

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To the Editor:
Telotristat ethyl, a tryptophan hydroxylase inhibitor, recently received Food and Drug Administration approval on February 28, 2017 for patients with carcinoid syndrome diarrhea that is refractory to somatostatin analog (SSA) therapy.1 The key article that was published earlier this year by Kulke et al2 showed that the drug resulted in clinically meaningful improvement in carcinoid syndrome diarrhea (“bowel movement frequency reduction ≥30% from baseline for ≥50% of the double-blind treatment period in more than 40% of the patients”). This translated into a mean reduction of approximately 2 bowel movements from baseline to week 12 of treatment. The drug was overall well tolerated with a good safety profile. No significant adverse events were reported other than mild nausea and asymptomatic increases in the γ-glutamyl transferase. The recent North American Neuroendocrine Tumor Society consensus statement published by Strosberg et al3 in the journal also deemed it a reasonable approach in patients with refractory carcinoid syndrome diarrhea patients.
Since its approval, we have had 3 patients with carcinoid syndrome symptoms refractory to SSA therapy where telotristat ethyl was prescribed. In all 3 instances, they had sudden onset of chest pain and hypertension that would be rated as grade 3 on the Common Terminology Criteria for Adverse Events version 4.0. In the first instance, the patient was a 67-year-old male and had taken the medication for 4 days. The second patient was a 55-year-old woman where symptoms started 3 days after initiation of the drug and again was associated with grade 3 hypertension. Her symptoms of diarrhea, which were in the range of 10 to 16 bowel movements a day, had significantly decreased to only 2 to 3 a day. Furthermore, the quality of life was better owing to less flushing episodes. However, the appearance of chest pain prompted discontinuation of the drug. In the third instance, this was noted a month later of the patient being prescribed the standard dose of 250 mg thrice a day. The patient apparently was only using the last week of monthly cycle of SSA and was on it for 7 days when he developed chest pain and worsening of underlying hypertension.
Looking back at the initial studies using the telotristat ethyl including the clinical trial published, there was only 1 report of a patient with grade 3 hypertension, but no reports of chest pain.4 There were 3 additional patients who also developed hypertension during treatment.
Postmarketing ongoing surveillance would be important to see if this is seen in other patients. Development of high blood pressure or worsening of underlying hypertension may be an early sign to monitor in the first several days of being prescribed the medication in patients with carcinoid syndrome.

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