Developments in the treatment of carcinoid syndrome – impact of telotristat
Bibliographic record
Abstract
Carcinoid syndrome occurs in 20% of patients with neuroendocrine tumors, and serotonin is usually the main causative hormonal peptide. Carcinoid syndrome, and particularly diarrhea, can significantly impact patients' quality of life. Somatostatin analogs (SSAs) are the mainstay of treatment, but are unable to ameliorate symptoms in all patients due to dose-limiting side effects and tachyphylaxis. Telotristat is a novel oral inhibitor of tryptophan hydroxylase, which is the rate-limiting enzyme in serotonin synthesis. A Phase III placebo-controlled trial of telotristat etiprate (orally at 250 mg three times a day) showed a significant decrease in the frequency of bowel motions in treated patients with diarrhea from carcinoid syndrome. The main side effects were gastrointestinal symptoms, deranged liver function tests and depression. Treatment with 500 mg three times a day also decreased stool frequency, but was associated with more nausea and mood disturbances. Telotristat, therefore, represents a valuable option in the management of carcinoid syndrome diarrhea refractory to SSAs, and the US Food and Drugs administration approved its use for this indication in March 2017. However, its role in somatostatin-naïve patients and in the treatment of other carcinoid syndrome symptoms (flushing and abdominal pain) remains unknown. Further research should focus on these issues as well as the safety of continuing telotristat in the context of other systemic antineoplastic therapies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".