Phase I and Pharmacokinetic Study of Novel <scp>l</scp>-Nucleoside Analog Troxacitabine Given as a 30-Minute Infusion Every 21 Days
Bibliographic record
Abstract
PURPOSE: Troxacitabine (Troxatyl, BCH-4556; BioChem Pharma Inc, Basingstoke, United Kingdom) is a novel synthetic L-nucleoside analog with activity against a broad range of human tumors in preclinical models. Preclinical toxicity suggested a predictable toxicity profile consistent with an agent of this class, with evidence of interspecies differences. We conducted a phase I study of troxacitabine given as a 30-minute infusion once every 21 days. PATIENTS AND METHODS: The starting dose of troxacitabine was 0.025 mg/m(2), based on toxicology data from the most sensitive species studied (cynomolgus monkey). Doses were doubled until grade 1 skin or mucosal or grade 2 other toxicity was encountered. A modified Fibonacci scale was used. RESULTS: A total of 45 patients were enrolled at 13 dose levels. Most common nonhematologic side effects were skin rash (44%), lethargy (29%), nausea (24%), alopecia, dry skin (18%), anorexia (13%), neurosensory symptoms (13%), and hand-foot syndrome (13%). In patients treated with prednisone 25 mg/d orally for 5 days, starting on day 1, skin rash was less problematic. Two patients at 12.5 mg/m(2) experienced dose-limiting (grade 4) granulocytopenia. Confirmed partial responses were documented in one patient with previously untreated renal cell carcinoma with metastatic lung and bone lesions and in one patient with an unknown primary tumor. Eighteen patients had a best response of stable disease with a median duration of 5.1 months (range, 2.1 to 18.7 months). CONCLUSION: When given in this schedule, the maximum-tolerated dose of troxacitabine is 12.5 mg/m(2), and the recommended dose for additional phase II studies is 10 mg/m(2) once every 21 days with steroid premedication.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".