Age-related effects on the pharmacodynamic (PD) relationship between STEALTH liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors

2576 Background: STEALTH liposomal CKD-602 (S-CKD602), a camptothecin analogue, is eliminated by the reticuloendothelial system (RES), which consists of cells including monocytes. CKD-602 released from S-CKD602 is eliminated by the kidney. Therefore, we evaluated the PD relationship between monocyte and absolute neutrophil counts (ANC; as a control) in blood and S-CKD602 and non-liposomal CKD-602 (NL-CKD602) in patients (pts) with refractory solid tumors. We also evaluated the effect of age on these relationships. Methods: In a phase I study, S-CKD602 was administered IV x 1 q 3 wk at 0.1 to 2.5 mg/m2. In phase I and II studies, NL-CKD602 was administered IV qdx5d q 3 wk at 0.5 to 0.9 mg/m2/d and 0.5 mg/m2/d, respectively. The % decreases in ANC and monocytes at nadir were calculated. For S-CKD602, pharmacokinetic studies of encapsulated (E), released (R), and sum total (ST=E+R) CKD-602 in plasma and ST in urine were performed and measured by LC-MS/MS. Area under the plasma concentration versus time curve...