Waning Control of Diarrhea 3 to 4 Weeks After Long-Acting Somatostatin Analogue Injection
Patients with neuroendocrine tumors (NETs) and carcinoid syndrome who are being treated with somatostatin analogue (SSA) therapy may still experience diarrhea due to any number of reasons. As such, the approach requires confirming the cause of the diarrhea first before considering interventions to control it.
Professor of Gastrointestinal Oncology
“For patients with NETs, carcinoid syndrome, and refractory diarrhea, our first question typically is whether the diarrhea is attributable to a hormonal syndrome.”
For patients with NETs, carcinoid syndrome, and refractory diarrhea, our first question typically is whether the diarrhea is attributable to a hormonal syndrome. There are many reasons why patients with NETs and carcinoid syndrome may have diarrhea. For example, they may have short bowel syndrome or bile acid malabsorption from a prior small-bowel surgery, or they may have pancreatic exocrine insufficiency from SSA injections. It is important to try to confirm that the patient's diarrhea is not from some other cause (eg, steatorrhea from pancreatic exocrine insufficiency) before concluding that it has a syndromic origin.
If it is determined that the patient's diarrhea is due to refractory carcinoid syndrome, and that their serotonin or urine 5-hydroxyindoleacetic acid levels are increasing while they are on an SSA, you move on to the second question. What can be done to treat the patient's diarrhea?
To improve hormone-related symptoms, sometimes increasing the dose or the frequency of a patient's SSA can help, especially if that individual is experiencing refractory symptoms toward the end of their 4-week cycle of a long-acting SSA injection. Some patients will benefit from increasing the frequency of their long-acting SSA injections from every 4 weeks to every 3 weeks. Additionally, the tryptophan hydroxylase inhibitor telotristat is an option for the treatment of refractory diarrhea in patients with carcinoid syndrome, with refractory diarrhea being defined as more than 4 bowel movements per day while on the SSA. While the benefits of telotristat therapy in these individuals tend to be modest, and it certainly does not work for everyone with carcinoid syndrome–related refractory diarrhea, it does seem to work well in a subset of patients.
If symptoms are occurring in conjunction with clinically significant radiographic progression, the primary management strategies are either liver embolization or peptide receptor radionuclide therapy with lutetium 177 dotatate. In patients with liver-dominant disease, liver embolization can be quite effective for controlling diarrhea. Moreover, in the NETTER-1 study, investigators reported a significant delay in diarrhea-related decline in quality of life with peptide receptor radionuclide therapy compared with high-dose octreotide therapy.
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