Pegylated Liposomal Doxorubicin and Vinorelbine in Recurrent Ovarian Carcinoma: A Pharmacokinetic Study on Alternate Administration Sequences

Abstract

Background: This multicenter pharmacokinetic study evaluated the pharmacokinetics and toxicity of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with recurrent ovarian cancer, when administered in opposing sequences. Patients and Methods: Eighteen heavily pre-treated ovarian cancer patients received treatment with PLD 30 mg/m² and VNR 30 mg/m² every 3 weeks for 6 cycles, 9 being given the PLD-VNR sequence vs. 9 the VNR-PLD sequence. Results: The VNR AUC_tot and plasma levels were considerably higher with the PLD-VNR sequence and VNR clearance, clearly related to K_el, was about half that occurring with VNR-PLD. Toxicity was generally mild and reversible. In both arms, a sound correlation was found between VNR AUC_tot and absolute neutrophil count decrease. A possible correlation between hematological toxicity and the 2 opposing administration sequences was also shown. Conclusion: The higher VNR AUC_tot and plasma levels during the elimination phase with the PLD-VNR sequence may be related to a P-gp membrane glycoprotein inhibition by PLD vescicles which, in turn, may influence the plasma level of the associated VNR. PLD-VNR, producing a higher plasma level and very mild toxicity, may be considered the preferred sequence.