Paclitaxel Pharmacokinetics and Response to Chemotherapy in Patients with Advanced Cancer Treated with a Weekly Regimen

Abstract

Background: Paclitaxel pharmacokinetics were shown to be related to toxicity and survival. Patients and Methods: We evaluated the effects of time above paclitaxel concentrations of 0.05 μmol/l (T_>0.05) and systemic exposures (AUC) to total and unbound paclitaxel (tPAC, uPAC) on response in patients with advanced cancer treated with weekly 1-h or 3-h infusions. Results: After 6 weeks of therapy (WOT), 13 out of 21 assessable patients showed either partial response (PR) or stable disease (SD), while 8 had progressive disease (PD). As compared to patients with PD, those with PR or SD showed similar AUCs to uPAC and tPAC but higher (p<0.05) T_>0.05. Patients with T_>0.05≥20.7 hours had lower probability (p<0.05) to progress within 12 WOT. Conclusion: Taking the heterogeneity of the studied tumor types into account, we found T_>0.05 to be associated with response to treatment. This emphasizes the value of threshold models for the investigation of paclitaxel pharmacodynamics.