Eflornithine for the Chemoprevention of Luminal Gastrointestinal Neoplasms: A Systematic Review
Bibliographic record
Abstract
Background: Gastrointestinal (GI) tract malignancies represent a significant global health burden, being major contributors to cancer-related morbidity and mortality globally, with over 7.7 million cases reported. While aspirin is a well-studied chemopreventive agent for GI neoplasms, its use may be limited due to the underlying bleeding risk. Eflornithine (DFMO) is an inhibitor of the ornithine decarboxylase (ODC) which inhibits polyamine synthesis, and has shown promise as an alternative chemopreventive agent, particularly in animal studies and limited clinical trials. Methods: Following PRISMA guidelines, we conducted a systematic review of studies evaluating DFMO alone or in combination for chemoprevention in premalignant GI lesions including chronic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia. The protocol was registered in Prospero (CRD42022309307). Randomized controlled trials (RCTs) and cohort studies in English or Spanish were included. Results: Nine studies (six RCTs and three phase I-II trials) met inclusion criteria. Phase I-II trials involving Barrett's esophagus and gastric cancer did not report significant benefits. Phase III-IV trials combining DFMO with nonsteroidal anti-inflammatory drugs (NSAIDs) were associated with reductions in adenoma recurrence, size, and polyamine levels in high-risk GI cancer populations. Side effects included ototoxicity, reversible upon discontinuation, and mild GI events, both occurring at higher doses. Conclusion: While aspirin remains a frontline chemopreventive agent for GI neoplasms, this review shows that phase III-IV trials suggest promising outcomes in combination with NSAIDs, warranting further investigation. Notably, DFMO's low cost and favorable toxicity profile may position it as a viable alternative, emphasizing the need for additional RCTs to delineate its efficacy and safety in GI cancer prevention. Further investigation into DFMO's optimal dosage, duration, and side effect management is essential to establish it as a safe and effective chemopreventive agent.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".