5-HT3 Receptor Blockers and Carcinoid Syndrome
Endoscope showing a carcinoid tumor in a patient's rectum / Science Source
Neuroendocrine tumors (NETs) represent a broad classification of cancers that derivate from poorly to well-differentiated cell lines.
One example of an NET is a carcinoid tumor, which is typically considered "well-differentiated" and resides primarily within the gastrointestinal (GI) tract.
Patients with carcinoid tumors sometimes experience a constellation of symptoms such as diarrhea, flushing, and shortness of breath. These symptoms are mediated by the chemical factors (e.g., serotonin, histamine, somatostatin, and dopamine) produced by their tumors. These symptoms as a whole are labeled as “carcinoid syndrome.”
Symptomatic relief of carcinoid syndrome often includes the use of the somatostatin analogs octreotide or lanreotide. These medications work to inhibit the factors secreted by the carcinoid tumor; however, these medications are relatively expensive and often require prior authorization approval, at which point they may be difficult to find as an outpatient.
Neither octreotide nor lanreotide are available in oral form and must be given subcutaneously or intramuscularly. The effect of the somatostatin analogs also may be only temporary in some patients, leading to a continued strain on their quality of life.1
Since many of the symptoms experienced in carcinoid syndrome are either primarily or secondarily mediated by serotonin, 5-HT3 receptor blockers such as ondansetron may play a role in symptomatic relief. There is only a limited amount of data studying the use of 5-HT3 receptor blockers in patients with carcinoid syndrome, but they do appear promising.
A study of only six patients currently receiving a somatostatin analog showed a decrease in bowel movements after administration of oral ondansetron.2 These patients were given 16 mg per day of ondansetron for 3 days, then titrated down to a maintenance dose between 4 mg and 8 mg per day.
Intravenous ondansetron has also been used with some limited success, as demonstrated in a small study of 11 patients who showed improvement in diarrhea and nausea with 24 mg of oral ondansetron given daily over the course of approximately 1 week.3
Patients with carcinoid syndrome represent a unique oncologic population with challenging symptoms. In addition to the traditional therapies that include somatostatin analogs, the 5-HT3 receptor blockers, such as ondansetron, may prove useful in controlling patients' symptoms, particularly with an oral formulation that can be given on an outpatient status. However, additional clinical data are needed in order to fully assess the role of 5-HT3 receptor blockers in carcinoid syndrome.
1. Modlin IM, Pavel M, Kidd M, et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010;31:169-188.
2. Kiesewetter B, Raderer M. Ondansetron for diarrhea associated with neuroendocrine tumors. N Eng J Med. 2013 May16:368(20): 1947-8.
3. Wymenga ANM, de Vries EGE, Lejisma MK, et al. Effects of ondansetron on gastrointestinal symptoms in carcinoid syndrome. Eur J Cancer. 1998;34:1293-4.