BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.     

Influence on binding of third-order torque to second-order angulation

Using an earlier model, which described the critical contact angle for binding from second-order angulation alone, a more generalized model is derived that combines the effects of angulation and torque. From this vantage point, the onset of binding is evaluated for 3 scenarios: second-order angulation alone, third-order torque only, and a combination of second-order angulation and third-order torque. These scenarios are detailed by plotting the critical contact angle for binding against the torque angle as a function of 10 wire dimensions (16 x 16, 16 x 22, 17 x 17, 17 x 22, 17 x 25, 18 x 18, 18 x 22, 18 x 25, 19 x 25, and 21 x 25 mil), 4 bracket widths (70, 100, 130, and 160 mil), and 4 bracket slots (18, 20.5, 22, and 24.5 mil). From these plots, we learn that each wire base dimension (eg, an 18-mil base as found in 18 x 18-mil, 18 x 22-mil and 18 x 25-mil archwires) has a common maximum critical contact angle for binding. Moreover, each wire-slot combination has a common maximum torque angle, which is independent of bracket width. Finally, we learn that archwire-bracket combinations that use a metric 0.5-mm slot might have some advantages with regard to torquing--given the current philosophy that light, continuous forces are more favorable.