A randomized phase II study of axitinib (AG-013736) and gemcitabine versus gemcitabine in advanced pancreatic cancer, preceded by a phase I component
Bibliographic record
Abstract
4551 Background: The current standard of care for patients (pts) with advanced pancreatic cancer (APC) is gemcitabine (GEM)- based chemotherapy. Axitinib (AG) is a potent inhibitor of vascular endothelial growth factor receptors. A phase I study of AG in solid tumors identified 5 mg BID as the therapeutic starting dose. The main objectives of this trial are to determine whether the overall survival (OS) of the combination of AG and GEM is superior to that of GEM alone as first-line therapy in pts with APC, and to determine doses of AG and GEM that can be safely administered together. Methods: 8 pts were treated on the phase 1 (P1) portion of this trial. For the phase 2 (P2) portion of the trial, 103 pts with locally advanced or metastatic disease, no prior GEM or VEGF/VEGFR inhibitors, PS 0–2 were randomized (2:1) to GEM 1,000 mg/m2 over 30 minutes on days (D) 1, 8, 15 every 28 D with or without AG at a starting dose of 5 mg po BID between Jan 06 and Aug 06. CT scans were performed every 2 cycles. Results: Data from the evaluable P1 pts (n=5) indicated that PK of GEM and AG appeared to be unchanged in combination. The GEM mean plasma exposure (AUC) was 11,348 alone vs 12,840 ng.h/mL with AG; similarly mean steady-state AG AUC was 250 alone vs 270 ng.h/mL with GEM. 3 of 8 pts had a PR. The median number of days on study drug was 158 days (range: 57–330 days) with 2 pts ongoing. Data from the randomized P2 pts: male 48%; median age 62 (36- 81); PS 0/1 vs 2: 91% vs 9%; 41% with locally advanced disease; 59% with metastatic disease. The most commonly reported adverse events are anemia (48%), alk phos elevations (48%), leukopenia (45%), neutropenia (42%), LFT elevations (39%), and thrombocytopenia (27%). The most common non-hematologic adverse events are nausea (24%), vomiting (20%), fatigue (19%), diarrhea (18%), anorexia (18%), constipation (13%), dyspnea (12%), and pyrexia (12%). 55 events have been reported in the 103 P2 pts. The pooled median OS is 203 days with a 95% CI of (158, not estimable). The median follow-up time is currently 223 days. Conclusions: AG can be safely administered at a starting dose of 5 mg BID in combination with standard dose GEM in patients with APC. Final safety and OS results by treatment arm will be presented. [Table: see text]
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".