IND.175: Phase I study of daily oral AZD2171, a vascular endothelial growth factor receptor inhibitor (VEGFRI), in combination with gemcitabine and cisplatin (G/C) in patients with advanced non-small cell lung cancer (ANSCLC): A study of the NCIC Clinical Trials Group
Bibliographic record
Abstract
7649 Background: AZD2171 is an oral an inhibitor of the tyrosine kinase activity of all VEGFR subtypes. Objectives: To determine recommended phase II dose (RPTD), dose limiting toxicity (DLT), toxicity, pharmacokinetics and efficacy of AZD2171 with G/C, in pts with untreated ANSCLC. Methods: Eligibility: stage IIIB/IV NSCLC; PS 0–2; no prior chemotherapy (CT) for advanced disease; adequate hematological, biochemical and end-organ function; no significant hemoptysis or bleeding. Treated stable brain metastases were permitted. G 1,250 mg/m2 day 1 & 8 and C 80 mg/m2 day 1 was given q3 weekly with AZD2171 starting day 2 cycle 1. Planned dose levels (DL) of AZD2171 were 30 and 45 mg once daily PK assayed in cycle 1&2, response (RECIST) every 2nd cycle. Results: 14 pts enrolled. 30 mg (5 pts) and 45 mg (9 pts). Pt characteristics (n=13) median age 56; 11 PS 0–1; 9 males. No DLTs seen in initial 3 pts at 30 mg dose; nor in 9 pts at 45 mg dose. Actual median dose intensity for AZD2171 in cycle 1 (C1) was similar to planned in C1 for both DL (200 mg and 300 mg)), but was higher for 30 mg vs 45 mg for subsequent cycles (150 mg vs 134 mg). At the 45 mg DL 13 dose reductions occurred in 9 pts. Grade 3 adverse events occurred in 2 of 3 30 mg pts (1 hypertension (HT), 1 fatigue); at 45 mg 6 pts of 9 pts had grade 3 events (HT, fatigue, diarrhea, voice changes); 2 pts had grade 4 toxicity (1 reversible CNS ischemia, 1 fatigue). PK: no effect of AZD2171 on gemcitabine PK Objective response: 9 pts are evaluable (4 too early At 30 mg-PR 2, SD 1; at 45 mg-PR 3, SD 3. 2 additional patients were accrued at the 30 mg DL. Conclusions: Toxicities of this combination are manageable and predictable. HT was easily controlled with a standardized treatment algorithm. MTD was not reached at the 30 or 45mg dose level, but 30mg of AZD2171 appears better tolerated in combination with G/C and is suggested as the RPTD. Encouraging anti-tumor activity has been observed which does not appear dose dependent at the doses tested. 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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.005 | 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".