Treatment Strategies in Neuroendocrine Tumors - Episode 4

Symptom Control in Functional NETs


Timothy J. Hobday, MD: Our patients with neuroendocrine tumors may produce various hormones that cause symptoms and troubles in their life. It can be a fascinating and diverse array of situations that they present with. One of the most common is carcinoid syndrome, typically from carcinoid tumors in the small intestine that produce serotonin and, perhaps, other biologic amines.

This classically causes diarrhea and flushing. It rarely may cause hypertension, wheezing, and other symptoms, but can be quite function limiting. With this, somatostatin receptor analogs, such as octreotide or lanreotide, often result with very significant improvements in symptoms and quality of life and can be quite useful.

Many patients with pancreatic neuroendocrine tumors, or neuroendocrine tumors of other primary sites, can produce a vast array of hormones. Some can cause life-threatening troubles such as issues with insulin, ACTH (adrenocorticotropic hormone), cortisol, vasoactive intestinal peptide, or other bothersome syndromes such as gastrin production, stomach acid troubles, and other various hormones. Sometimes, they can produce 1, 2, or 3 different hormones that affect them. In that situation, somatostatin receptor antagonists can be helpful. However, I find it less likely that we significantly improve difficult symptoms than we do in the carcinoid syndrome.

So, for all these patients, if they are not well palliated by somatostatin receptor antagonists, we can look to try to give therapy that may reduce the tumor bulk. Whether this be systemic chemotherapy, regional therapies that go after large metastatic lesions in the liver, surgical therapy, or peptide receptor radiotherapy, the goal would be to kill as many tumor cells as possible, to reduce the production of the hormones and significantly palliate our patient’s symptoms.

Carcinoid syndrome is a description of symptoms that often arise from the serotonin production in patients with carcinoid tumors. It often consists of flushing, diarrhea, and, occasionally, other symptoms such as hypertension and wheezing. Sometimes patients will experience fainting spells. That’s carcinoid syndrome.

Prolonged carcinoid syndrome can scar and thicken, impacting the ability of the valves in the right side of the heart to function well. They leak, threatening the function of the right side of the heart. That’s a very severe complication called carcinoid heart disease. Occasionally patients with carcinoid syndrome can have carcinoid crisis, which is an abrupt hemodynamic instability brought on, we think, by a massive discharge of serotonin that is usually triggered by general anesthesia, perhaps hepatic artery embolic therapies, and other emergent situations.

Heloisa P. Soares, MD: The quality of life of patients with neuroendocrine syndrome, when the syndrome is not very well controlled, can be impacted and affected by the disease. These patients can have a significant amount of diarrhea per day. Some of my patients reported that they have more than 10 bowel movements a day with, perhaps, explosive diarrhea. They cannot leave the house. They cannot have a functional life. So, controlling the symptoms is very, very important. They also may have a lot of flushing, which can be uncomfortable as well. In cases of typical carcinoid syndrome symptoms, you can have bronchospasm, which you see in lung patients. Controlling that with medications that we have available, or interventions such as surgery or embolization of the liver, is very important to try to minimize the carcinoid syndrome and improve the quality of life of these patients.

Jonathan R. Strosberg, MD: Neuroendocrine tumors are often characterized by the propensity to produce hormones. The most common one is carcinoid syndrome, which is predominantly caused by serotonin secretion but also by other vasoactive substances. Somatostatin analogs are really the cornerstone of symptom control. They’ve been used for many years, for various hormonal symptoms—not just carcinoid syndrome, which is characterized by flushing, diarrhea, and other, rarer hormonal syndromes associated with pancreatic neuroendocrine tumors, such as the VIPomas, glucagonomas, and gastrinomas.

Beyond that, there are other treatments that can be used for symptom control. There’s a serotonin inhibitor called telotristat (Xermelo) that’s used for refractory diarrhea associated with carcinoid syndrome. It’s an oral serotonin inhibitor, and it’s quite effective at reducing diarrhea in patients who remain uncontrolled despite the use of somatostatin analogs.

It’s also important to consider many other causes of diarrhea that patients may experience. For example, pancreatic malabsorption can be caused by either somatostatin analogs or, in some cases, by pancreatic surgery. It’s important to consider bile malabsorption, often caused by right hemicolectomy, short bowel syndrome. So, there are many other factors involved that we need to consider.

Transcript Edited for Clarity