Age-Related Changes in Nanoparticle Albumin-Bound Paclitaxel Pharmacokinetics and Pharmacodynamics: Influence of Chronological Versus Functional Age

Purpose.This study evaluated age-related changes in pharmacokinetic and pharmacodynamic parameters of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with metastatic breast cancer. Methods. Forty patients received nab-paclitaxel (100 mg/m 2 weekly for 3 weeks followed by a 1-week break) as first- or second-line chemotherapy. Blood samples were collected for analysis, and response was assessed every two cycles. Planned statistical analyses included linear regression to examine the relationship between age and pharmacokinetic variables (ln clearance[CL]andlnareaunderthecurve[AUC])andtwo-sided two-sample t tests to evaluate age differences in pharmacodynamic variables. The association between chemotherapy toxicityriskscoresandpharmacokineticandpharmacodynamic variables including grade $3 toxicity were examined post hoc. Results. Of 40 patients enrolled, 39 (98%) were evaluable (mean age: 60 years; range: 30–81 years). A partial response was achieved in 31%, and 38% had stable disease.There was a borderline positive association between age and 24-hour ln AUC(slope50.011;SE50.006;p5.055).Grade3toxicitywas