A study of effects of concomitant administration of proton pump inhibitors (PPIs) and capecitabine (cape) on survival in early stage colorectal cancer (CRC) patients (pts).
Bibliographic record
Abstract
e17688 Background: Cape is used to treat CRC and other cancers. Many pts take PPIs for symptom control. TRIO-013, a study of cape/oxaliplatin +/- lapatinib in metastatic gastro-esophageal cancer, failed to show an increase in overall survival (OS). Ad hoc analysis of PPI effects in both arms showed negative impact on cape efficacy with PPI use. This study’s objectives are to report effects of PPIs on cape efficacy in early stage CRC and to explore how cape dose adjustments for toxicity impact survival outcomes. Methods: A retrospective study of all pts diagnosed with early stage CRC treated with adjuvant cape monotherapy between 2008 and 2012 was undertaken at the Cross Cancer Institute, Edmonton, Canada. Data was collected on demographics, medications, toxicities, and pt outcomes. Results: 298 pts were identified with 129 pts taking PPIs and 169 pts not taking PPIs. PPI pts had lower 5-yr OS rate vs. non-PPI pts – 72% vs 85% (HR 2.01, 95% CI 1.14-3.56, p = 0.02). 5- yr recurrence free survival (RFS) was 71% in PPI pts vs. 88% in non-PPI pts (HR 2.57, 95% CI 1.45-4.56, p-value = 0.001). Adjusting for age, gender, stage and ECOG, PPI pts still had poorer OS (HR 1.88, 95% CI 1.04-3.41, p = 0.04) and RFS (HR 2.24, 95% CI 1.25-4.04, p = 0.007). Cape dose modifications also impacted outcomes. Pts with dose delays due to toxicity had better 5-yr OS 90% vs. pts with no toxicity 82% vs. pts with toxicity requiring dose reductions 73% (p = 0.02). Corresponding 5-yr RFS was 100% vs. 84% vs. 67% (p = 0.006). Conclusions: PPIs impair cape efficacy possibly by altering gastric pH, preventing cape tablet dissolution, and therefore absorption, consistent with findings in TRIO-013. As oral anti-cancer therapies become more prevalent, in addition to food effect studies, phase I PPI-drug interaction studies are necessary to avoid negative impact on patient outcomes. In addition, pts with dose delays due to toxicity had better outcomes than pts with no toxicity and with dose reductions, suggesting toxicity from cape may be beneficial.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".