Evaluation of body surface area (BSA) based dosing, age, and body composition as factors affecting the pharmacokinetic (PK) variability of STEALTH liposomal doxorubicin (Doxil)

C107 Introduction: The prescribed dose of anticancer agents is most commonly calculated using body surface area (BSA) as the only independent variable; however, it has been shown that this approach still results in large interpatient variability in drug exposure. Baker et.al, reported that BSA should not be used in dose calculations of several anticancer agents and that alternative dosing strategies should be evaluated (JNCI’02). The dose of STEALTH liposomal doxorubicin (Doxil) is also based on BSA. However, using BSA based dosing for Doxil still results in significant interpatient variability in plasma exposure. We previously reported that patients (pts) ≥ 60 years old (yo) have a reduced clearance (CL) of STEALTH liposomal CKD-602 (S-CKD602), a camptothecin analogue, compared with pts Methods: Pharmacokinetic studies of Doxil were determined as part of phase I and II studies of in pts with solid tumors (n = 23) and in pts with AIDS-related Kaposi’s sarcoma (KS) (n = 37). Doxil was administered at doses of 10 to 60 mg/m 2 IV every 28 days. The CL of sum total (encapsulated and released) doxorubicin as estimated by L/h/m 2 and L/h were calculated for each patient by non-compartmental methods. We used the suggested criteria by Baker et.al to determine whether BSA-dosing was associated with a reduction in interpatient variability in Doxil CL: 1) a linear regression coefficient between BSA and Doxil CL (L/h) (R 2 ≥ 0.25); 2) P Results: The linear regression coefficient between BSA and Doxil CL (L/h) was R 2 = 0.18 (P = 0.04). The relative reduction in variability of CL was 11%. Mean ± SD Doxil CL in pts with solid tumors that were 2 , respectively (P = 0.001). Mean ± SD Doxil CL in pts with KS that were 2 and was similar to solid tumor patients Conclusion: These results suggest that the use of BSA based dosing for Doxil does not sufficiently reduce the large interpatient variability in drug exposure. In addition, this study suggests that alternate dosing strategies should be evaluated for Doxil. This data also suggests that pts ≥ 60 yo have a lower Doxil CL compared with pts