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- Strosberg, J., et al.
(författare)
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Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 376:2, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials. gov number, NCT01578239; EudraCT number 2011-005049-11.)
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- Rindi, G., et al.
(författare)
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TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.
- 2006
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 449:4, s. 395-401
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Forskningsöversikt (refereegranskat)abstract
- The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.
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- Strosberg, Jonathan, et al.
(författare)
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Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate : an analysis of the NETTER-1 study
- 2020
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 47:10, s. 2372-2382
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with Lu-177-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the Lu-177-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions Lu-177-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. : NCT01578239, EudraCT: 2011-005049-11
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- Caplin, M. E., et al.
(författare)
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Pulmonary neuroendocrine (carcinoid) tumors : European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:8, s. 1604-1620
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. Patients and methods: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. Results: PCs are well-differentiated neuroendocrine tumors and include low-and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. Conclusions: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.
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- Ambrosini, Valentina, et al.
(författare)
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Use and perceived utility of [18 F]FDG PET/CT in neuroendocrine neoplasms : A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
- 2024
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Ingår i: Journal of neuroendocrinology. - 0953-8194 .- 1365-2826. ; 36:1, s. e13359-
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Tidskriftsartikel (refereegranskat)abstract
- Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
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| 32. |
- Anthony, Lowell B., et al.
(författare)
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Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome
- 2019
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Ingår i: The Oncologist. - : WILEY. - 1083-7159 .- 1549-490X. ; 24:8, s. E662-E670
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome. Subjects, Materials, and Methods Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated. Results Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4. Conclusion Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. Implications for Practice Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.
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| 33. |
- Bodei, Lisa, et al.
(författare)
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Molecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy
- 2020
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 21:9, s. E431-E443
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Forskningsöversikt (refereegranskat)abstract
- Peptide receptor radionuclide therapy (PRRT) is a type of radiotherapy that targets peptide receptors and is typically used for neuroendocrine tumours (NETs). Some of the key challenges in its use are the prediction of efficacy and toxicity, patient selection, and response optimisation. In this Review, we assess current knowledge on the molecular profile of NETs and the strategies and tools used to predict, monitor, and assess the toxicity of PRRT. The few mutations in tumour genes that can be evaluated (eg, ATM and DAXX) are limited to pancreatic NETs and are most likely not informative. Assays that are transcriptomic or based on genes are effective in the prediction of radiotherapy response in other cancers. A blood-based assay for eight genes (the PRRT prediction quotient [PPQ]) has an overall accuracy of 95% for predicting responses to PRRT in NETs. No molecular markers exist that can predict the toxicity of PRRT. Candidate molecular targets include seven single nucleotide polymorphisms (SNPs) that are susceptible to radiation. Transcriptomic evaluations of blood and a combination of gene expression and specific SNPs, assessed by machine learning with algorithms that are tumour-specific, might yield molecular tools to enhance the efficacy and safety of PRRT.
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| 34. |
- Gonzalez-Quiroz, M., et al.
(författare)
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Rationale and population-based prospective cohort protocol for the disadvantaged populations at risk of decline in EGFR (CO-DEGREE)
- 2019
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A recently recognised form of chronic kidney disease (CKD) of unknown origin (CKDu) is afflicting communities, mostly in rural areas in several regions of the world. Prevalence studies are being conducted in a number of countries, using a standardised protocol, to estimate the distribution of estimated glomerular filtration rate (eGFR), and thus identify communities with a high prevalence of reduced glomerular filtration rate (GFR). In this paper, we propose a standardised minimum protocol for cohort studies in high-risk communities aimed at investigating the incidence of, and risk factors for, early kidney dysfunction. Methods and analysis This generic cohort protocol provides the information to establish a prospective population-based cohort study in low-income settings with a high prevalence of CKDu. This involves a baseline survey that included key elements from the DEGREE survey (eg, using the previously published DEGREE methodology) of a population-representative sample, and subsequent follow-up visits in young adults (without a pre-existing diagnosis of CKD (eGFR<60 mL/min/1.73m 2), proteinuria or risk factors for CKD at baseline) over several years. Each visit involves a core questionnaire, and collection and storage of biological samples. Local capacity to measure serum creatinine will be required so that immediate feedback on kidney function can be provided to participants. After completion of follow-up, repeat measures of creatinine should be conducted in a central laboratory, using reference standards traceable to isotope dilution mass spectrometry (IDMS) quality control material to quantify the main outcome of eGFR decline over time, alongside a description of the early evolution of disease and risk factors for eGFR decline. Ethics and dissemination Ethical approval will be obtained by local researchers, and participants will provide informed consent before the study commences. Participants will typically receive feedback and advice on their laboratory results, and referral to a local health system where appropriate. © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
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| 39. |
- Modlin, Irvin M., et al.
(författare)
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Gastroenteropancreatic neuroendocrine tumours
- 2008
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 9:1, s. 61-72
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Forskningsöversikt (refereegranskat)abstract
- Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.
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| 41. |
- O'Callaghan-Gordo, Cristina, et al.
(författare)
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Prevalence of and risk factors for chronic kidney disease of unknown aetiology in India : Secondary data analysis of three population-based cross-sectional studies
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess whether chronic kidney disease of unknown aetiology (CKDu) is present in India and to identify risk factors for it using population-based data and standardised methods. Design Secondary data analysis of three population-based cross-sectional studies conducted between 2010 and 2014. Setting Urban and rural areas of Northern India (states of Delhi and Haryana) and Southern India (states of Tamil Nadu and Andhra Pradesh). Participants 12 500 individuals without diabetes, hypertension or heavy proteinuria. Outcome measures Mean estimated glomerular filtration rate (eGFR) and prevalence of eGFR below 60 mL/min per 1.73 m 2 (eGFR <60) in individuals without diabetes, hypertension or heavy proteinuria (proxy definition of CKDu). Results The mean eGFR was 105.0±17.8 mL/min per 1.73 m 2. The prevalence of eGFR <60 was 1.6% (95% CI=1.4 to 1.7), but this figure varied markedly between areas, being highest in rural areas of Southern Indian (4.8% (3.8 to 5.8)). In Northern India, older age was the only risk factor associated with lower mean eGFR and eGFR <60 (regression coefficient (95% CI)=a '0.94 (0.97 to 0.91); OR (95% CI)=1.10 (1.08 to 1.11)). In Southern India, risk factors for lower mean eGFR and eGFR <60, respectively, were residence in a rural area (a '7.78 (-8.69 to -6.86); 4.95 (2.61 to 9.39)), older age (a '0.90 (-0.93 to -0.86); 1.06 (1.04 to 1.08)) and less education (a '0.94 (-1.32 to -0.56); 0.67 (0.50 to 0.90) for each 5 years at school). Conclusions CKDu is present in India and is not confined to Central America and Sri Lanka. Identified risk factors are consistent with risk factors previously reported for CKDu in Central America and Sri Lanka.
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| 43. |
- Strosberg, Jonathan R., et al.
(författare)
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NETTER-1 phase III : Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate
- 2016
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Ingår i: Journal of Clinical Oncology. - Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Kentucky, Lexington, KY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vet Adm Med Ctr, Iowa City, IA USA. Royal Free Hosp, Pond St, London NW3 2QG, England. Zent Klin Bad Berka, Bad Berka, Germany. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Univ Uppsala Hosp, Uppsala, Sweden. Adv Accelerator Applicat, New York, NY USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Beaujon Hosp, Clichy, France. Erasmus MC, Rotterdam, Netherlands.. - 0732-183X .- 1527-7755. ; 34:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 44. |
- Strosberg, Jonathan R., et al.
(författare)
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Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with 177Lu-DOTATATE
- 2021
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:12, s. 1712-1718
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Tidskriftsartikel (refereegranskat)abstract
- We report the impact of 177Lu-DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors often find burdensome.Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures.Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 d per 4 wk, respectively, compared with 0.99, 1.44, and 2.54 d for high-dose octreotide LAR. The mean differences were 3.11 d (95% CI, 1.35–4.88; P = 0.0007) for abdominal pain, 3.11 d (1.18–5.04; P = 0.0017) for diarrhea, and 1.98 d (0.08–3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated-measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing.Conclusion: In addition to efficacy and quality-of-life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu-DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut neuroendocrine tumors, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu-DOTATATE on health-related quality of life.
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| 45. |
- Weickert, Martin O., et al.
(författare)
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Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
- 2018
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 40:6, s. 952-962
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In the placebo-controlled Phase III TELE-STAR (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 [1.1), 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.
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