The role of serotonin inhibition within the treatment of carcinoid syndrome

by Selleckchem | Nov 04 2023

Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It was first reported in 1954, and the classical symptoms are diarrhoea, flushing and abdominal pain. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. Therefore, the focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patient's quality of life. There are a variety of management options for carcinoid syndrome including medical, surgical and loco-regional interventional radiological procedures. The most widely used are somatostatin analogues with three clinically approved drugs: lanreotide and octreotide (first-generation) and pasireotide (second-generation). Both everolimus and interferon used in combination with octreotide have shown significant reduction in urinary 5-hydroxyindoleacetic acid compared to octreotide alone. Telotristat ethyl has been increasingly utilised for patients with symptoms despite taking somatostatin analogues. It has also been shown to have a significant improvement in bowel movement frequency which was associated with a significant improvement in quality of life. Peptide receptor radionuclide therapy has proven symptomatic improvement in patients with uncontrolled symptoms. Chemotherapy is primarily reserved for patients with high proliferation tumours, with limited research on the efficacy in reducing symptoms. Surgical resection remains the optimal treatment due to being the only one that can achieve a cure. Liver-directed therapies are considered in patients where curative resection is not possible. There are therefore numerous different therapies. This paper describes the pathophysiology and therapy of carcinoid syndrome.

Comments:

Carcinoid syndrome is indeed the most frequent hormonal complication associated with neuroendocrine neoplasms. It was first reported in 1954, and its classical symptoms include diarrhea, flushing, and abdominal pain. The syndrome is caused by the secretion of various vasoactive substances, with serotonin being the most prominent, contributing to the clinical symptoms that characterize carcinoid syndrome. Therefore, the primary focus of treatment for carcinoid syndrome is to reduce serotonin production and improve the patient's quality of life.

There are several management options available for carcinoid syndrome, including medical, surgical, and loco-regional interventional radiological procedures. Among the medical treatments, somatostatin analogues are widely used. There are three clinically approved drugs in this class: lanreotide, octreotide (first-generation), and pasireotide (second-generation). These analogues work by inhibiting the release of various hormones, including serotonin, from neuroendocrine tumors, thus alleviating the symptoms associated with carcinoid syndrome.

In addition to somatostatin analogues, combination therapies have shown promising results. Everolimus and interferon, when used in combination with octreotide, have demonstrated a significant reduction in urinary 5-hydroxyindoleacetic acid (a metabolite of serotonin) compared to octreotide alone. Telotristat ethyl is another medication that has been increasingly used for patients who continue to experience symptoms despite taking somatostatin analogues. It has been shown to significantly improve bowel movement frequency, which is associated with an improvement in the quality of life for these patients.

For patients with uncontrolled symptoms, peptide receptor radionuclide therapy (PRRT) has shown symptomatic improvement. PRRT involves the administration of a radioactive substance that binds to the receptors on neuroendocrine tumor cells, delivering radiation directly to the tumor. This targeted approach can help alleviate symptoms and improve the patient's well-being.

Chemotherapy is typically reserved for patients with high-proliferation tumors, although its efficacy in reducing symptoms is limited and requires further research.

Surgical resection remains the optimal treatment option for carcinoid syndrome, as it is the only approach that can potentially achieve a cure. However, not all patients are suitable candidates for surgery, especially if the tumor has spread to distant sites. In such cases, liver-directed therapies, such as embolization or radiofrequency ablation, may be considered to target the tumors in the liver and help control symptoms.

In summary, the management of carcinoid syndrome involves a variety of therapeutic options, including medical treatments with somatostatin analogues and other medications, loco-regional interventional radiological procedures, and, when feasible, surgical resection. The choice of therapy depends on factors such as tumor characteristics, symptom severity, and patient-specific considerations. A multidisciplinary approach involving oncologists, endocrinologists, surgeons, and interventional radiologists is crucial to tailor the treatment to the individual patient and provide the best possible outcomes.