Paclitaxel pharmacokinetics and response to chemotherapy in patients with advanced cancer treated with a weekly regimen

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 mu mol/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.