A phase II study of BAY 43–9006 in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal cancer (NPC)
Bibliographic record
Abstract
5566 Background: Bay 43–9006, a novel bi-aryl urea, is a potent inhibitor of kinases of Raf-1 (C-Raf) and B-Raf which are critical members of the RAS/RAF/MEK/ERK signalling pathway. In addition, Bay 43–9006 inhibits other pro-angiogenic protein tyrosine kinases, including VEGFR-2/3 and PDGFR-β. Overexpression of these signal transduction and angiogenic markers has been associated with poor prognosis in epithelial malignancies. We conducted a phase II study to examine the efficacy of Bay 43–9006 in advanced HNSCC and NPC. Methods: Patients (pts) with advanced HNSCC and NPC with measurable disease, no more than one prior chemotherapy regimen for recurrent and/or metastatic disease, performance status (PS) ECOG 0–2, and adequate organ functions were eligible. Bay 43–9006 was administered orally at 400 mg BID on a continuous basis, in 28-day cycles. Responses were evaluated every 8 weeks according to RECIST criteria. Results: Seventeen patients have been enrolled to date (9m/8f). Median age was 59 years (range 46 - 77); 82% had PS 0 or 1 and 18% PS 2; 65% HNSCC and 35% NPC; 11 pts had received prior chemotherapy, 3 had received prior erlotinib and 16 had received prior radiation therapy. All pts were evaluable for toxicity and 10 for response assessment to date. Six pts (60%) (4 HNSCC and 2 NPC) had stable disease ranging from 3 to 6 cycles, and 4 pts (40%) had progressive disease. A total of 36 cycles had been administered (median number/patient: 2; range 1–6). No grade 4 toxicity was seen. Main haematological toxicity was grade 3 lymphopenia in 5 (29%) pts. Common grade 3 non-hematological toxicity included hyponatremia in 4 (24%), dyspnea in 3 (18%), and non-specific pain in 3 (18%) pts. Grade 1/2 non-hematolgical toxicity included fatigue in 15 (88%), hypertension in 6 (35%), hand-foot syndrome in 6 (35%) and skin rash in 3 (18%) pts respectively. One pt died of intracranial tumoral hemorrhage, deemed to be unlikely related to treatment. Conclusions: Bay 43–9006 was well tolerated. Although no objective response was seen to date in this group of heavily pretreated patients, over half of the evaluable patients had achieved tumor stabilization. Further trial accrual is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".