4CPS-035 Association of dihydropyrimidine dehydrogenase deficiency with capecitabine tolerance
Bibliographic record
Abstract
Background and Importance Dihydropyrimidine dehydrogenase (DPD) is the first of the enzymes in the fluoropyrimidine metabolic pathway. Recently, the Spanish Agency of Medicine and Health Products reported an informative note warning that patients with partial or total deficiency in DPD activity cannot adequately degrade fluoropyrimidines, increasing the risk of serious toxicity. DPD genotyping is recommended as standard practice for predicting the occurrence and severity of capecitabine toxicity. Aim and Objectives To assess the rate of deficiency of the metabolising enzyme DPD in patients treated with capecitabine and to describe the associated toxicity. Material and Methods A retrospective observational study was conducted during 2022 in a regional hospital. Age, gender, Eastern Cooperative Oncology Group (ECOG) and diagnosis were collected from the electronic clinical history. To determine the variants of DPD, a pharmacogenomics analysis was performed using a real-time polymerase chain reaction technique. The polymorphisms studied were rs3918290, rs55886062, rs67376798 and rs56038477. Regarding the management of patients, the doses reduction, adverse events (AE), and withdrawal treatments were recorded. Results Thirty-six patients were included with median age 70.9 (50–88) years. ECOG 0–1 was observed in 94% of cases. Capecitabine was used for the following diagnoses: colorectal cancer (n=22, 61%), gastric cancer (n=9, 25%) and breast cancer (n=5, 14%). DPD genotyping was performed on 25 patients (69%). A mutated allele heterozygote was detected in 3 (8.3%) patients: rs56038477 (n=2, 5.5%) and rs67376798 (n=1, 2.8%). A 50% dose reduction was prescribed initially according to pharmacogenetics recommendations in DPD deficiency and this dose was maintained throughout the entire treatment. In patients without mutation a dose reduction was required in 8 (32%). All patients with DPD mutation and 20 (80%) without DPD mutation presented AE. The most common AE in this population were weakness (n=18, 50%), diarrhoea (n=17, 47.2%), gastrointestinal such as nausea (n=10, 27.8%), dactylitis (n=8, 22.2%), mucositis (n=8, 22.2%), paraesthesia (n=8, 22.2%),hyperpigmentation (n=6, 16.7%) and constipation (n=4,11.1%). Six (16.7%) discontinuations of capecitabine due to AE were reported. Conclusion and Relevance It is important to know the DPD polymorphism to correctly adjust the capecitabine dose. A considerable percentage of patients without DPD mutation report AE. Determination of variants of DPD can help avoid serious or fatal EA. References and/or Acknowledgements Conflict of Interest No conflict of interest
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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 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".