A phase I study of DX 8951f (exatecan mesylate for injection) in patients with renal dysfunction

2069 Background: Exatecan mesylate is a novel camptothecin analog. Neutropenia and thrombocytopenia are its dose limiting toxicities (DLTs). Although the drug appears to be predominately cleared by the liver, the impact of renal dysfunction on its pharmacokinetic profile is unknown. Methods: A dose escalation study was performed with patients (pts) treated in pre-defined cohorts of renal dysfunction determined by 24-hour measured urine creatinine clearance - CrCL (Table 1). Once a DLT was observed, pts were stratified by prior therapy (heavily pre-treated-HP versus minimally pre-treated- MP). Exatecan was given daily x 5 every 21 days. Results: 32 pts have been accrued to this study. The number of DLT events observed for each group are: Normal - 1/6 pts at 0.5 mg/m2; Mild −1/7 HP pts at 0.4 mg/m2; Moderate −1/3 HP pts and 0/3 MP pts at 0.4 mg/m2and 1/1 MP pt at 0.5 mg/m2; Severe −0/2 HP pts at 0.1 mg/m2. The mean total CL of exatecan per body surface area (BSA) for each group is presented in Table 1 and r...