Phase II Trial of a Metronomic Schedule of Docetaxel and Capecitabine with Concurrent Celecoxib in Patients with Prior Anthracycline Exposure for Metastatic Breast Cancer
Bibliographic record
Abstract
BACKGROUND: This phase ii clinical trial examined the activity of a metronomic dosing schedule of docetaxel and capecitabine chemotherapy in patients with advanced breast cancer. Patients also received daily oral celecoxib in an effort to improve outcome measures and to ameliorate some of the common side effects of chemotherapy. METHODS: Patients received docetaxel at a starting dose of 15 mg/m² weekly, oral capecitabine 1250 mg/m² once daily, and oral celecoxib 200 mg twice daily. The primary endpoint was clinical benefit: percentage of patients experiencing either an objective response or stable disease (sd) for more than 6 months. In the absence of significant neutropenia, the dose of docetaxel was escalated after 4 and 8 weeks of treatment. Therapy was given until disease progression or development of unacceptable toxicity. The level of thymidine phosphorylase expression in peripheral white blood cells of patients was measured before and during treatment to determine the effect on this capecitabine-activating enzyme. RESULTS: Of 47 patients enrolled, 38 (81%) completed treatment to a disease endpoint. No complete responses were achieved, but 13 of the 38 patients (34%) experienced a partial response, and another 3 patients (8%) experienced sd for more than 6 months. The clinical benefit rate was therefore 42% (95% confidence interval: 27% to 57%). The median time to disease progression for all evaluable patients was 3.6 months (range: 0.9-21.7 months). The most common nonhematologic toxicities were diarrhea, plantar- palmar erythrodysesthesia, fatigue, mucositis, and vomiting. Most patients (89%) received combination chemotherapy until disease progression. CONCLUSIONS: The present study demonstrates that metronomic docetaxel-capecitabine chemotherapy with daily celecoxib can produce significant anticancer activity, with predictable toxicity. Efficacy fell short of expectations, with outcome measures being similar to those obtained when the study agents are given in conventional dosing. Furthermore, there is mounting evidence to indicate that a low dose of taxanes fails to induce thymidine phosphorylase expression, an effect believed to be important in achieving therapeutic synergism when taxanes are given concurrently with capecitabine.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Randomized trial | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | medium |
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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, unvalidatedLabeled directly by 2 models reading the full record.
The models disagree on parts of this classification; every voice is preserved in the section at the end of the page.
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".