Phase I Trial of 72-Hour Continuous Infusion UCN-01 in Patients With Refractory Neoplasms

摘要: PURPOSE: To define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of novel protein kinase inhibitor, UCN-01 (7-hydroxystaurosporine), administered as a 72-hour continuous intravenous infusion (CIV). PATIENTS AND METHODS: Forty-seven patients with refractory neoplasms received during this phase I trial. Total, free plasma, salivary concentrations were determined; latter used to address influence plasma binding on peripheral tissue distribution. The phosphorylation state C (PKC) substrate alpha-adducin abrogation DNA damage checkpoint also assessed. RESULTS: recommended II CIV is 42.5 mg/m2/d for 3 days. Avid UCN-01, measured trial, dictated change in escalation administration schedules. Therefore, nine drug initial 2-week schedule, 38 4-week schedule. DLTs at 53 m...