A multi-centre phase II trial of pegylated liposomal doxorubicin and trastuzumab in HER-2 over-expressing metastatic breast cancer (MBC)
Bibliographic record
Abstract
630 Background: Although combination therapy with conventional doxorubicin and trastuzumab (H) improves clinical outcome in HER-2 + MBC, a 27% cardiac dysfunction rate prevents clinical use of this combination. In a large phase III trial in MBC, pegylated liposomal doxorubicin (PLD:Caelyx®) was equally efficacious as conventional doxorubicin, but with significantly less cardiotoxicity. As well, the combination of PLD and H are synergistic in multiple breast cancer cell lines. With this rationale we performed a phase II trial of the combination of PLD and H as 1st line therapy in HER-2 + MBC, with cardiac safety as the primary end-point. Methods: Patients with measurable HER-2 + (IHC3+ or FISH positive) MBC were treated with PLD at 50 mg/m2 every 4 weeks and H at a 4 mg/kg loading then 2 mg/kg weekly. Left ventricular ejection fraction (LVEF) was assessed by MUGA at baseline and after every 2nd cycle. Prior adjuvant anthracycline exposure was allowed. Cardiac toxicity was defined as either a LVEF decline ≥ 15% regardless of absolute value; decline ≤ 10% with absolute LVEF < 45%; or symptomatic congestive heart failure (CHF). Results: 30 patients were enrolled from Aug 01 –Sept 03 from 4 Canadian centres. The median age was 59 years (31–75 years). 83% of the patients had visceral metastases, 64% had ER+ tumours and 41% had received prior adjuvant anthracyclines. A median of 5 cycles of PLD has been delivered so far (range 1–9). The mean LVEF at baseline, following cycles 2 and 4 were 63%, 59% and 60% respectively. A total of 3 patients experienced protocol-defined cardiotoxicity. No patient experienced symptomatic CHF. 27% of patients experienced grade 3 palmar-plantar erythrodysesthesia. The response rate (RR) for the evaluable cohort (n=29) was 55%. Within the 17 patients with no prior anthracycline exposure the RR was 65%. Median TTP and OS have not yet been reached. Conclusions: The combination of PLD and H is an active combination as 1st line therapy in HER-2 over-expressing MBC, with limited cardiotoxicity. This promising combination warrants further evaluation in the treatment of HER-2 over-expressing breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering Canada Schering Canada Schering Canada Hoffmann LaRoche; Schering-Plough
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".