Serotonin synthesis inhibitors: a novel approach for managing gastrointestinal symptoms in carcinoid syndrome Abstract #121

Introduction: Carcinoid syndrome (CS) occurs when metastatic carcinoid tumors secrete large amounts of serotonin (5-HT) and other bioactive substances into systemic circulation, causing a variety of symptoms, including GI symptoms such as profound diarrhea. Reduction in 5-HT production by the tumor would be expected to improve symptoms in patients with CS.
Aim(s): To examine the utility of inhibiting tryptophan hydroxylase (TPH), the enzyme that catalyzes the rate-limiting step in the synthesis of 5-HT, as a strategy to reduce 5-HT production in vivo with the goal of developing a new therapeutic approach to CS. The ability of LX1031 and LX1032, two novel TPH inhibitors, to reduce 5-HT production was determined in clinical trials.
Materials and methods: Single and multiple ascending dose studies with LX1031 and LX1032 were conducted in normal volunteers. In addition, a 28-day study was conducted with the locally acting TPH inhibitor LX1031 in patients with non-constipating IBS. In the IBS study, multiple measures of GI symptoms were recorded daily, along with a weekly global assessment. In all studies, blood and urine were collected for measurement of 5-HT and 5-HIAA, biomarkers of 5-HT production.

To read results and conclusion, please login ...

Further abstracts you may be interested in

#28 Prognostic Clinicopathologic Factors in Longitudinally Followed Patients with Metastatic Small Bowel Carcinoid
Introduction: Neuroendocrine tumors demonstrate heterogeneous behavior based upon site of origin and specific histology. Even after controlling for anatomic location, disease stage and histologic grade, registry studies show persistent diversity of outcome in patients with midgut carcinoid.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Mr. Thomas Curran
#29 Serum chromogranin A correlation with tumor burden in metastatic small bowel carcinoid patients
Introduction: Patients with neuroendocrine tumors may have clinical courses that range from fairly indolent to more aggressive. Cross–sectional studies, nuclear imaging and biochemical markers are often used to monitor disease progression. Optimal surveillance tests and intervals have not been firmly established. Studies suggest that chromogranin A (CgA) may be a surrogate marker for tumor burden.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Mr. Thomas Curran
#255 The Carcinoid Syndrome Caused by Retroperitoneal Carcinoid Tumors
Introduction: The carcinoid syndrome is caused by increased levels of serotonin and is mostly seen in cases of carcinoid tumor in the small bowel and liver metastases, as there is a very high first pass effect.
Conference: 8th Annual ENETS Conference (2011)
Category: Clinical
Presenting Author: Dr Benedicte V Wilson
Authors: Wilson B, Nielsen H O, ...
#304 Hepatic Neuroendocrine Tumor Metastasis Proliferation is Hepatocyte Regulated Via a 5HT7 Mediated Induction of an IGF 1 and HGF Feedback Loop Mediated by cAMP, PKA-independent pAKT and pCREB
Introduction: Carcinoid serotonin (5-HT) causes local fibrosis but the effect of 5-HT on hepatocytes has not been established. We hypothesized that tumors and hepatocytes form a metastasis-supportive environment.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: Dr Mark Kidd
Authors: Svejda B, Kidd M, Lawrence B, Alaimo D, ...
#394 Efficacy of Telotristat Etiprate in Refractory Carcinoid Syndrome: Results of a Randomized, Placebo-controlled, Multicenter Study
Introduction: Diarrhea associated with carcinoid syndrome (CS) has been attributed to excess serotonin. Telotristat etiprate is an oral serotonin synthesis inhibitor that decreases peripheral serotonin production.
Conference: 9th Annual ENETS Conference (2012)
Category: Clinical
Presenting Author: Dr. Matthew Kulke
Close
Notice

WARNING – FRAUDULENT WEBSITES

ENETS is aware that its members have been confronted with fake websites, which seem to relate to our congress but have not been commissioned or authorised by us. The websites offer fraudulent hotel reservation services. We therefore strongly recommend that you please only use the official enetsconference.org website when booking your tickets and accommodation. Please be vigilant when it comes to providing your credit card details. 

If you have any questions, please do not hesitate to contact us at info@enets.org.