Telotristat for Diarrhea in Patients With Carcinoid Syndrome
Telotristat represents a new treatment option that may decrease diarrhea incidence with a relatively safe side effect profile.
Carcinoid syndrome is the collection of symptoms generally caused by factors secreted by neuroendocrine tumors (NETs). NETs are typically found in the gastrointestinal (GI) tract and lungs, and secrete a myriad of compounds including serotonin, histamine, and dopamine.1-3
As up to 40 compounds are secreted by NETs, the clinical presentation varies depending on the secreted hormone. Carcinoid syndrome is most frequently seen in patients with liver metastases at time of presentation.
Patients with carcinoid syndrome frequently experience flushing, hypotension, and diarrhea. Excess serotonin is implicated in diarrhea by causing increased GI secretions and motility; histamine and kallikrein contribute to the significant flushing experienced by these patients.
Diarrhea occurs in close to 80% of patients with carcinoid syndrome. The diarrhea is typically secretory in nature, where patients will experience over one liter of watery (non-bloody) stool per day, nocturnal symptoms, and continuation of diarrhea despite fasting. If stool studies are collected, these patients will typically have an osmotic gap of less than 50 mOsm/kg.
Somatostatin analogs such as octreotide are used to treat these patients experiencing significant diarrhea. Octreotide act as an anti-secretory agent that inhibits the secretion of multiple hormones by NETs.
Recently, a new medication, telotristat, was developed as combination therapy with octreotide for patients with carcinoid syndrome–related diarrhea. Telotristat inhibits the conversion of tryptophan to serotonin, which is one of the primary mediators of diarrhea in carcinoid syndrome.4,5