Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: The primary objective of this study was to determine whether addition of the selective P-glycoprotein (P-gp) inhibitor tariquidar (XR9576) to chemotherapy could induce an objective tumor response in patients who previously were resistant to the same agents. The secondary objectives were to evaluate P-gp expression by immunohistochemistry (IHC), to determine functional activity of the P-gp transporter before and after administration of tariquidar with serial technetium-99m ((99m)Tc)-sestamibi scans, and to correlate those parameters with clinical response. METHODS: Seventeen women with Stage III-IV breast carcinoma were included in the study who progressed (n = 13 women) or had stable disease (n = 4 women) on doxorubicin-containing or taxane-containing chemotherapy regimens. During the study, the same chemotherapy was continued without dose modifications, but tariquidar (150 mg intravenously) was added to the treatment regimen. RESULTS: Thirty-six percent of patients had P-gp-positive tumors by IHC, and 5 patients (29%) experienced increases > or = 10% in sestamibi uptake (median increase, 40%; range, 10-63%) after the administration of tariquidar. There was one partial response in a patient who had the greatest increase in sestamibi uptake and who also showed inducible P-gp expression. There was one patient who experienced severe doxorubicin/docetaxel-related toxicity after tariquidar was added to her chemotherapy regimen. CONCLUSIONS: Tariquidar showed limited clinical activity to restore sensitivity to anthracycline or taxane chemotherapy. Functional imaging of the tumor with (99m)Tc-sestamibi scans before and after administration of multidrug-resistance inhibitor may be useful to identify the small subset of patients who could benefit from multidrug-resistance modulation in future trials.
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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) | 0.000 | 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 it