Generalizability of results from oncology clinical trials: Toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer
Bibliographic record
Abstract
6633 Background: The relevance of oncology clinical trial results in clinical practice depends on whether the trial participants are similar to the entire population of patients with the malignancy and whether the patients are treated similarly in both circumstances. Irinotecan treatments are associated with high rates of severe diarrhea, and may be even more toxic in patients with poor performance status and advanced age, who are usually not included in clinical trials. Methods: A retrospective chart review was performed including all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy (irinotecan monotherapy, FOLFIRI, IFL, XELIRI) from January 2004 to September 2006 at Juravinski Cancer Centre, Hamilton, Ontario, Canada. We aimed to determine the toxicity of these irinotecan regimens in clinical practice compared to those published in corresponding large phase 2 and 3 clinical trials. The primary endpoint was incidence of grade 3/4 diarrhea. A subgroup analysis of elderly patients older than 75 years of age was also conducted. Results: A total of 206 patients met our inclusion criteria and were included in the analysis. 18 patients (9%) were older than 75 years of age, while 21 (10%) and 7 (3%) had an ECOG performance status of 2 and 3, respectively. The rates of grade 3/4 diarrhea for FOLFIRI (n = 103), IFL (n = 14), irinotecan monotherapy (n = 71) and XELIRI (n = 18) were 11%, 14%, 21% and 17%, respectively, compared to 10% (Colucci, 2005), 23% (Saltz, 2000), 31% (Saltz, 2000) and 20% (Patt, 2007) in the clinical trials. The rates of grade 3/4 neutropenia in our study were 22%, 14%, 18% and 11%, respectively. The number of patients with at least one hospital admission for adverse effects from irinotecan chemotherapy were 11%, 21%, 18% and 6%, respectively. The incidence of grade 3/4 diarrhea in patients 75 years of age and younger was 15% compared to 11% for patients older than 75 years of age. Conclusions: Overall, the toxicity rates of irinotecan chemotherapy in non-trial patients do not appear to be in excess of those quoted in published clinical trials. This may be due to a cautious patient selection process on the part of the prescribing oncologists at our institution. No significant financial relationships to disclose.
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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 | 0.279 | 0.583 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".