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Purpose: Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose. Patients and Methods: Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m2 loading dose; 250 mg/m2 maintenance dose weekly) + cisplatin (100 mg/m2 every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Fifteen patients completed a median (range) of 8.7 (2.0–20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related n = 4). TEAEs (N = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N = 15) showed mean (SD) AUC0–21d of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N = 15) was 47%. Median (95% confidence interval) PFS and OS (N = 15) were 7.9 (3.7–9.7) and 13.5 (6.6–17.5) months, respectively. Conclusions: Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen.

Engaging clinicians in practice development initiatives can be a daunting task, especially if those staff groups are spread over a five-site NHS Trust. Within Sheffield Teaching Hospitals NHS Foundation Trust (STHFT), the geography across the city adds a unique dimension to bringing about changes in practice and using the best possible evidence. Specific strategies need to be put in place in order to enable clinicians to access specialist help within the Trust, using the available networks to their best advantage and thereby reducing repetition. The role of a practice development team situated within such a large organization can influence changes in practice and encourage newer innovative ways of working. Copyright © 2009 John Wiley & Sons, Ltd.

We present a chromosome classifier for automated karyotyping of banded chromosomes which uses a multi-layer perception neural network. Two network configurations have been investigated. The resulting classifiers have been trained and tested on data from three different data sets covering a range of data quality. Classification results compare very favourably with those obtained using a highly optimised parametric classifier.