Phase I Dose-Finding Study of a New Taxane, RPR 109881A, Administered as a One-Hour Intravenous Infusion Days 1 and 8 to Patients With Advanced Solid Tumors
Bibliographic record
Abstract
PURPOSE: To define the maximum-tolerated dose, recommended phase II dose (RD), dose-limiting toxicity (DLT), and pharmacokinetics of a novel taxane, RPR 109881A, administered on days 1 and 8 of a 21-day cycle. PATIENTS AND METHODS: Twenty-nine patients were enrolled and treated according to a modified continual reassessment method from a starting dose of 7.5 mg/m(2) to 52.5 mg/m(2). Detailed pharmacokinetic analyses of blood and urine were performed on days 1 and 8 of the first cycle. Toxicity was monitored weekly. RESULTS: DLT consisting of grade 3 or 4 diarrhea was seen in three of six patients at 52.5 mg/m(2). Grade 3 or 4 granulocytopenia was also seen in five of six patients treated at this dose (four of six in the first cycle). At the next lower dose level, 45 mg/m(2) toxicity was moderate, with only one of 12 patients experiencing severe diarrhea and grade 4 granulocytopenia with associated infection. Drug concentrations were consistent with a three-compartment open model. The total-body clearance suggests a linear dose-concentration relationship. RPR 109881A has a high clearance (mean, 42.6 L/h/m(2)), a large volume of distribution (mean, 952 L/m(2)), and a long terminal half-life (mean, 24 hours). There was no drug accumulation between days 1 and 8. One partial response was seen in a patient with renal cell carcinoma. CONCLUSION: The RD of RPR 109881A given as a 1-hour infusion on days 1 and 8 of a 21-day cycle is 45 mg/m(2). At this dose the drug is well tolerated and should be further studied.
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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) | 0.002 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".