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/m(2) and VNR 30 mg/m(2) every 3 weeks for 6 cycles, 9 being given the PLD-VNR sequence vs. 9 the VNR-PLD sequence. Results: The VNR AUC(101) 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(101) 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(101) 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 higherplasma level and very mild toxicity, may be considered the preferred sequence.
Pegylated liposomal doxorubicin and vinorelbine in recurrent ovarian carcinoma: a pharmacokinetic study on alternate administration sequences
CATTEL, Luigi;MILLA, Paola;FERRERO AM
2006-01-01
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/m(2) and VNR 30 mg/m(2) every 3 weeks for 6 cycles, 9 being given the PLD-VNR sequence vs. 9 the VNR-PLD sequence. Results: The VNR AUC(101) 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(101) 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(101) 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 higherplasma level and very mild toxicity, may be considered the preferred sequence.
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