

FREQUENT, AND WATERY STOOLS
Functioning neuroendocrine tumors (NETs) can lead to a constellation of symptoms known as carcinoid syndrome (CS)1-4
CSD is the most common manifestation of CS and is caused primarily by serotonin overproduction from functioning NETs.1
Serotonin
Serotonin normally plays a role in mediating secretion and motility of the gastrointestinal tract, but excessive serotonin in the body can have significant physiologic consequences in multiple systems, including1-4:
- Flushing of the skin
- Bronchial constriction
- Tissue fibrosis and heart valve damage, potentially leading to carcinoid heart disease
Long-term SSA therapy alone can be ineffective in a majority of patients3,5-9


- Over time, tachyphylaxis and other mechanisms of resistance can lead to a diminished response to SSA therapies, and subsequent release of serotonin5
- This means that many patients can continue to experience debilitating diarrhea3,10,11
The combination of XERMELO + SSA offers 2 distinct pathways to reduce excess serotonin by addressing the underlying pathology3,10


- XERMELO inhibits the enzyme tryptophan hydroxylase, which reduces the production of serotonin3,10
- Together, XERMELO + SSA mediate serotonin overproduction by modifying its production AND release6,10


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References:
- Naraev B, Halland M, Halperin DM, Purvis AJ, O’Dorisio TM, Halfdanarson TR. Management of diarrhea in patients with carcinoid syndrome. Pancreas. 2019;48(8):961-972.
- Clement D, Ramage J, Srirajaskanthan R. Update on pathophysiology, treatment, and complications of carcinoid syndrome. J Oncol. 2020;2020:1-11.
- Molina-Cerrillo J, Alonso-Gordoa T, Martínez-Sáez O, Grande E. Inhibition of peripheral synthesis of serotonin as a new target in neuroendocrine tumors. Oncologist. 2016;21(6):701-707.
- Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-1015.
- Kulke MH, O’Dorisio T, Phan A, et al. Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer. 2014;21(5):705-714.
- SANDOSTATIN® LAR DEPOT (octreotide acetate) Prescribing Information. Novartis Pharmaceuticals Corporation.
- Janson ET, Öberg K. Long-term management of the carcinoid syndrome treatment with octreotide alone and in combination with alpha-interferon. Acta Oncologica. 1993;32(2):225-229.
- Toumpanakis C, Garland J, Marelli L, et al. Long-term results of patients with malignant carcinoid syndrome receiving octreotide LAR. Aliment Pharmacol Ther. 2009;30(7):733-740.
- Khan MS, El-Khouly F, Davies P, Toumpanakis C, Caplin ME. Long-term results of treatment of malignant carcinoid syndrome with prolonged release lanreotide (somatuline autogel). Aliment Pharmacol Ther. 2011;34(2):235-242.
- XERMELO® (telotristat ethyl) Prescribing Information. TerSera Therapeutics LLC.
- Kvols LK, Oberg KE, O’Dorisio TM, et al. Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Endocr Relat Cancer. 2012;19(5):657-666.