Telotristat ethyl: a new option for the management of carcinoid syndrome.
Many patients with neuroendocrine tumour-related carcinoid syndrome treated with somatostatin analogues (SSA) won't achieve adequate symptom relief with the SSA alone; new treatment options are required. Telotristat ethyl is a tryptophan hydroxylase inhibitor, developed for the treatment of carcinoid syndrome. Areas covered: This review summarises the evidence supporting the role of telotristat ethyl in the management of carcinoid syndrome. Rationale, pharmacodynamics, pharmacokinetics, metabolism, clinical experience, efficacy and toxicity profiles are covered. Expert opinion: The efficacy of telotristat ethyl in producing a statistically-significant and clinically-meaningful reduction in daily bowel movements has been confirmed in phase III clinical trials. Two pivotal trials, TELESTAR and TELECAST, explored the role of telotristat ethyl in the management of patients with carcinoid syndrome refractory to SSAs focusing on patients with ≥4 and <4 daily bowel movements, respectively. In addition, benefit was confirmed in patient-reported outcomes. Based on activity and safe toxicity profile, telotristat ethyl is pending regulatory agencies evaluation and is likely to add to the armamentarium used to treat carcinoid syndrome. Long-term safety and efficacy data will be available from the ongoing TELEPATH study. The impact on carcinoid heart disease, mesenteric fibrosis and other long-term complications of carcinoid syndrome as well as its role earlier in patients' pathways remain investigational.
a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.
Angela
A
Lamarca
a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.|b Faculty of Medical, Biological and Human Sciences , University of Manchester , Manchester , UK.
Jorge
J
Barriuso
a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.|c Institute of Cancer Sciences , University of Manchester , Manchester , UK.
Mairéad G
MG
McNamara
a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.
Richard A
RA
Hubner
a Department of Medical Oncology , The Christie NHS Foundation Trust , Manchester , UK.|c Institute of Cancer Sciences , University of Manchester , Manchester , UK.
Juan W
JW
Valle
D000818:Animals; D002276:Carcinoid Tumor / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D008303:Malignant Carcinoid Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011743:Pyrimidines; C000592493:telotristat; D010649:Phenylalanine; D013004:Somatostatin; C000621725:telotristat ethyl; D014365:Tryptophan Hydroxylase
Bowel movement; LX1606; carcinoid syndrome; diarrhoea; flushing; neuroendocrine tumours; serotonin synthesis inhibitor; telotristat ethyl; tryptophan hydroxylase 1 (Tph1)