A Pilot Pharmacokinetic and Antiangiogenic Biomarker Study of Celecoxib and Low-dose Metronomic Vinblastine or Cyclophosphamide in Pediatric Recurrent Solid Tumors
Bibliographic record
Abstract
Tumor vasculature is a reasonable target for cancer therapy and lower more frequent doses of traditional chemotherapeutics [low-dose metronomic (LDM) chemotherapy] has been shown to have antiangiogenic efficacy. This study evaluated the safety and pharmacokinetics of celecoxib and LDM vinblastine or cyclophosphamide in children with recurrent, refractory solid tumors. We also investigated whether a subset of circulating plasma proteins are surrogate markers of angiogenic activity. Thirty-three children were enrolled in this pilot study and received celecoxib (250 mg/m(2) PO b.i.d.) and either vinblastine (1 mg/m(2) IV 3 x /wk) or cyclophosphamide (30 mg/m(2) PO daily) continually. Celecoxib alone and with LDM chemotherapy was well tolerated and plasma concentrations were consistent with those shown to have antiangiogenic activity. Four patients (13%) had durable stable disease (28 to 78 wk) although no complete or partial responses were observed. The surrogate markers measured (vascular endothelial growth factor, basic fibroblast growth factor, soluble vascular cell adhesion molecule, soluble intercellular cell adhesion molecule, endostatin, and thrombospondin-1) were highly variable and no statistically significant relationship between them and disease progression or maintenance of stable disease was observed. We concluded that this regimen is well tolerated hence supporting the use of this form of therapy in pediatric patients. However, future studies should include more homogenous patient populations and focus on validating surrogate markers to monitor treatment activity.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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, 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".