Year: 2018
Type: article
Abstract: Purpose In 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/m 2 ) 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. Methods Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan. Findings In 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. Implications Up 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.
Source: Clinical Therapeutics
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
Institutions: National Health Service, University Hospital Coventry, University Hospitals Coventry and Warwickshire NHS Trust, Zentralklinik Bad Berka, Lexicon Pharmaceuticals (United States), Friedrich-Alexander-Universität Erlangen-Nürnberg, Charité - Universitätsmedizin Berlin, University of Manchester, The Royal Free Hospital, University of California, San Francisco, Stanford Medicine, Stanford University, University of Kentucky, MD Anderson Cancer Center Madrid, Uppsala University Hospital, Hospices Civils de Lyon, Hôpital Edouard Herriot, Kings Health Partners, King's College Hospital, Dana-Farber Cancer Institute
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,240
OpenAlex ID: W2799914583