Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome |
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| Authors: | Martin O Weickert Gregory Kaltsas Dieter Hörsch Pablo Lapuerta Marianne Pavel Juan W Valle Martyn E Caplin Emily Bergsland Pamela L Kunz Lowell B Anthony Enrique Grande Kjell Öberg Staffan Welin Catherine Lombard-Bohas John K Ramage Ashwin Kittur Qi M Yang Matthew H Kulke |
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| Institution: | 1. The ARDEN NET Centre, ENETS Centre of Excellence, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry, United Kingdom;2. Zentralklinik Bad Berka, Bad Berka, Germany;3. Lexicon Pharmaceuticals Inc, The Woodlands, Texas;4. Charité-Universitätsmedizin, Berlin, Germany;5. Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;6. University of Manchester/The Christie National Health Service Foundation Trust, Manchester, United Kingdom;7. Neuroendocrine Tumour Unit, European Neuroendocrine Tumor Society Centre of Excellence, Royal Free Hospital, London, United Kingdom;8. University of California, San Francisco, San Francisco, California;9. Stanford University School of Medicine, Stanford, California;10. University of Kentucky, Lexington, Kentucky;11. MD Anderson International Cancer Center, Madrid, Spain;12. Uppsala University Hospital, Uppsala, Sweden;13. Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France;14. King’s Health Partners European Neuroendocrine Tumor Society Centre of Excellence, King’s College Hospital, London, United Kingdom;15. Dana-Farber Cancer Institute, Boston, Massachusetts |
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| Abstract: | PurposeIn the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean SD] age, 63.5 8.9] years; mean SD] body mass index, 24.9 4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.MethodsAssessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.FindingsIn 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.ImplicationsUp to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors. ClinicalTrials.gov identifier: NCT01677910. |
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| Keywords: | carcinoid syndrome carcinoid syndrome diarrhea malnutrition neuroendocrine tumor telotristat ethyl weight |
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