Faculty Bibliography

OBJECTIVE: The primary objective of this study was to determine the rate of response to matuzumab in patients with recurrent, EGFR-positive ovarian, or primary peritoneal cancer. Secondary end points included safety and tolerability, time to tumor progression, duration of response, and overall survival. METHODS: A multi-institutional single arm phase II trial. RESULTS: Of 75 women screened for the study, 37 were enrolled and treated. Median age of the treated patient population was 58 years, and most patients had more than four prior lines of chemotherapy. Therapy was well tolerated, the most common toxicities being a constellation of skin toxicities, including rash, acne, dry skin, and paronychia, as well as headache, fatigue, and diarrhea. Serious adverse events were very rare but included a single episode of pancreatitis that may have been drug related. All patients completed therapy, receiving 1 to 30 infusions of matuzumab. There were no formal responses (RR=0%, 95% CI: 0-9.5%), although 7 patients (21%) were on therapy for more than 3 months with stable disease. CONCLUSIONS: Matuzumab at the dose and schedule selected is well tolerated. In this population of very heavily pretreated patients with epithelial ovarian and primary peritoneal malignancies, there was no evidence of significant clinical activity when matuzumab was administered as monotherapy.

The robustness of control is a requirement to maintain a fluid layer at conductive equilibrium heated to a highly supercritical condition. Robustness determines how much uncertainties, or design parameter mismatches, can be tolerated. Both linear stability analysis and three-dimensional fully nonlinear simulations are used for the study of the linear quadratic Gaussian (LQG) controller. The parameter mismatches from the nominal conditions are introduced into the plant model, while the LQG compensator assumes nominal conditions. The mismatches arise from boundary properties, actuator lag, sensor level uncertainty, and wall thickness, as well as from the major parameters such as Prandtl number, Rayleigh number, wave number, and truncation number in the reduced-order model. The results suggest that the LQG compensator action can preserve closed-loop stability at over ten times the critical Rayleigh number, provided that the mismatches in the sensor level and wall thickness are small. Mismatches in the Prandtl number and wall material properties have little impact. Mismatches in Rayleigh number and wave number are relatively benign compared with the sensor and thickness parameters. Techniques for measuring the plant output temperature at multiple levels with sufficient accuracy may be an implementation challenge.