A randomized phase II study of cediranib (CED) alone versus CED plus dasatinib (DAS) in patients (pts) with castration-resistant prostate cancer (CRPC).
Bibliographic record
Abstract
5039 Background: Activation of the Vascular Endothelial Growth Factor Receptor (VEGFR) and the oncogenic Src pathway has been implicated in the development of CRPC in preclinical models. CED and DAS are multi-kinase inhibitors targeting VEGFR and Src respectively. Phase II studies of CED (Karakunnel et al ASCO 2009) and DAS (Yu et al Urology 2011) in CRPC have shown single agent activity. Methods: Docetaxel-preteated CRPC pts were randomized to arm A: CED alone (20 mg/day) vs arm B: CED (20 mg/day) plus DAS (100 mg/day) given orally on 4-week cycles. Primary endpoint was 12 week progression-free survival (PFS) as per the Prostate Cancer Clinical Trials Working Group (PCWG2). Patient reported outcomes were evaluated using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Present Pain Intensity (PPI) scales. Correlative studies of bone turnover markers (BTM), including bone alkaline phosphate (BAP) and serum beta-C telopeptide (B-CTx) were serially assayed. Results: 22 patients, 11 per arm, were enrolled. Baseline demographics were similar in both arms. Median number of cycles = 4 in arm A (range 1-12) and 2 in arm B (range 1-9). Twelve-week PFS was 73 % in arm A vs 18 % in arm B (p = 0.03). Median PFS in months (arm A vs B) was: 5.2 vs 2.6 (95% CI: 1.9-6.5 vs 1.4-not reached). Most common grade 3 toxicities were hypertension, anemia and thrombocytopenia in arm A and hypertension, diarrhea and fatigue in arm B. One treatment-related death (retroperitoneal hemorrhage) was seen in arm A. FACT-P and PPI scores did not significantly change in either arm. No correlation between BTM and PFS was seen in both arms A and B. Conclusions: Although limited by small numbers, this randomized study showed that the combination of VEGFR and Src targeted therapy did not result in improved efficacy and may be associated with a worse outcome than VEGFR targeted therapy alone in pts with CRPC. Clinical trial information: NCT01260688.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.008 | 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".