A Phase I Study Of Flavopiridol Using An Alternative Schedule In Patients (Pts) With Advanced Solid Tumors

2580 Background: A phase I study of flavopiridol, a cyclin-dependent kinase inhibitor, using an alternative schedule was conducted in pts with solid tumors given its promising activity in pts with chronic lymphocytic leukemia (CLL). Methods: Using standard 3x3 ph I dose escalation design, NCI-sponsored trial was performed to determine the safety and dose-limiting toxicity (DLT) of flavopiridol given as a 30-min IV loading dose followed by a 4-hr infusion weekly for 4 wks repeated every 6 wks. DLT was defined as Gr 4 hematologic toxicity (HT) for \u003e 7 days, \u003e Gr 3 non-HT except Gr 3 fatigue or diarrhea resolving Gr 3 despite steroids. Blood samples were obtained at pre-dose and 0.5, 1, 3, 4.5, 6, 8, 24, and 48-hr after start of first bolus dose for pharmacokinetics (PK). Results: 26 pts with advanced solid tumors with a median age of 63 (44–75) yrs were enrolled. Median no. of doses was 7.5 (1–24). Table 1 outlines the PK parameters, DLTs and CRS. Due to a grade...