A phase I study of ABT-751 in combination with docetaxel in patients with metastatic hormone-refractory prostate cancer
Bibliographic record
Abstract
4651 Background: ABT-751 (A) is a novel oral sulfonamide anti-microtubule agent with broad-spectrum preclinical activity including paclitaxel-resistant tumors and additive effect with docetaxel (D). Dose-limiting toxicities (DLTs) with ABT-751 include peripheral neuropathy, ileus, and fatigue. The recommended phase II single-agent dose for a 21/28-day schedule is 200 mg/day. Methods: Patients (pts) with hormone-refractory prostate cancer (HRPC), ECOG performance status ≤ 2, and adequate organ function were eligible. D was administered intravenously on day 1 and A was administered orally once daily on days 1–14 of a 21-day cycle for a maximum of 10 cycles. Starting dose was 60 mg/m2 D and 100 mg A; escalated in 4 dose levels (DLs) to 75 mg/m2 D and 200 mg A. Pts received 10 mg oral prednisone daily. Plasma for PK analyses was obtained. Results: 18 pts have been enrolled (3 pts/DL1, 3 pts/DL2, 6 pts/DL3, 6 pts/DL4), 17 pts are currently evaluable: median age 66 years, median PSA 250 μg/L, metastatic sites to bone and/or lymph nodes (17), visceral (2), prior chemotherapy 5 pts. The median number of treatment cycles was 6 (range 2–10). 2 pts experienced DLT (1 febrile neutropenia/DL 3 and 1 diarrhea/grade 4 neutropenia at DL4); these dose levels were expanded to 6 pts with no further DLT. Hematologic toxicities include febrile neutropenia (2 pts), grade 3/4 neutropenia (7 pts). Additional non-hematologic toxicities were grade 1/2 beside 1 episode of grade 3 diarrhea and lethargy each. AUC and Cmax for A were similar to single-agent data. AUC and Cmax for D appeared independent of ABT-751 dosing. PSA decline of ≥50% occurred in 10/16 evaluable pts (63%), ≥30% in 14/16 pts (89%) and <30% in 2/16 pts as best response thus far. Best response per RECIST in 12 pts with measurable disease was partial response in 4 pts (33%) and stable disease in 8 pts (67%). Conclusions: The combination of ABT-751 and docetaxel is well tolerated at the tested doses. PK results suggest no significant PK interaction. Early findings indicate encouraging clinical activity of the combination treatment. Extended accrual to the recommended phase II dose is ongoing to further define activity and toxicity. No significant financial relationships to disclose.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".