Pegylated liposomal doxorubicin and vinorelbine in recurrent ovarian carcinoma: a pharmacokinetic study on alternate administration sequences.
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.


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 AUCtot and plasma levels were considerably higher with the PLD-VNR sequence and VNR clearance, clearly related to Kel, was about half that occurring with VNR-PLD. Toxicity was generally mild and reversible. In both arms, a sound correlation was found between VNR AUCtot and absolute neutrophil count decrease. A possible correlation between hematological toxicity and the 2 opposing administration sequences was also shown.


CONCLUSIONS
The higher VNR AUCtot 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.
Cattel
Luigi
L
Dipartimento di Scienza e Tecnologia del Farmaco, Unità di Ginecologia Oncologica, Ospedale Mauriziano, Università di Torino, Italy. luigi.cattel@unito.it
Passera
Roberto
R
Katsaros
Dyonissios
D
Medail
Maurizio
M
Milla
Paola
P
Ferrero
Anna Maria
AM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D000077235:Vinorelbine
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine