Final results of a phase I study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor receptors (VEGFR), in combination with carboplatin (C) + paclitaxel (T) in patients with advanced non-small cell lung cancer (NSCLC): A study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)
Bibliographic record
Abstract
3054 Background: AZD2171 is a potent oral inhibitor of the tyrosine kinase activity of all VEGFR subtypes. This study was undertaken to determine the recommended phase II dose of AZD2171 in conjunction with standard doses of C and T, and to assess the tolerability, safety, PK profile and anti-tumor activity of this combination. Methods: Patients with stage IIIB / IV NSCLC (any histology); PS 0–2; no prior chemotherapy for metastatic disease and no significant hemoptysis / bleeding, were eligible. Treated, clinically stable brain metastases were permitted. C - AUC 6, and T - 200 mg/m2 over 3 hours, q3weekly. AZD2171 commenced day 2 cycle 1 at a starting dose of 30 mg po daily. PK profile of all was drugs performed during cycles 1 and 2. Response was assessed by RECIST every second cycle. Results: 20 patients were enrolled: AZD2171 30 mg (9 pts) and 45 mg (11 pts). Median age 58; 19 PS 0 / 1; 8 females. At 30 mg, one confirmed DLT was observed (grade 3 ALT); hypertension ≥ grade 2 was seen in 6 pts, prompting the institution of a standardized algorithm for management of this predictable toxicity. Of the first 3 pts enrolled to the 45 mg dose level, one DLT was observed (grade 3 febrile neutropenia with grade 3 mucositis); no further DLT was observed in the expanded cohort. Other common toxicities: fatigue, anorexia, mucositis and diarrhea. Hematologic toxicity was not greater than that expected with CT alone. No hemoptysis was seen. To date, 15 pts are evaluable for response: 6 PR, 8 SD and 1 PD. Many SD pts had evidence of tumor shrinkage, including central cavitation. Conclusions: Toxicities of this combination appear manageable and predictable. Full single-agent dose of AZD2171 may be administered with standard C+T. Hypertension, a typical toxicity of inhibitors of VEGF signaling, was observed but manageable. Encouraging anti-tumor activity of the combination has been observed. NCIC CTG BR.24, a phase II/III trial of C+T with AZD2171/placebo is underway. [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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".