Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma.
BACKGROUND
This multicenter phase II study evaluated feasibility, clinical efficacy, toxicity and pharmacokinetics of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with platinum-paclitaxel pretreated recurrent ovarian cancer.


METHODS
All patients received prior treatment with platinum and paclitaxel. Thirty-two heavily pretreated (median number of chemotherapy regimens two, range one to six) ovarian cancer patients received treatment with PLD 30 mg/m(2) and VNR 30 mg/m(2) every three weeks for six cycles. Ten patients entered the pharmacokinetic study, five receiving the PLD-VNR and five the VNR-PLD sequence.


RESULTS
In 30 patients evaluated for response and toxicity, the overall response rate was 37% and 10% of patients achieved stable disease. Median time to progression and overall survival were 5.5 months (range 1-10) and 9 months (range 2-16), respectively. Toxicity was generally mild and reversible. VNR AUC(tot) and plasma levels were considerably higher in the PLD-VNR sequence.


CONCLUSIONS
The PLD-VNR regimen exhibits significant activity in heavily pretreated patients, is well tolerated and is associated with encouraging survival. Preliminary pharmacokinetic results suggest the PLD-VNR sequence for further clinical applications. This regimen should be considered as a treatment option in patients with chemotherapy-resistant ovarian cancer.
Katsaros
D
D
Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Via Ventimiglia 3, 10126 Turin, Italy. dhocc@libero.it
Oletti
M V
MV
Rigault de la Longrais
I A
IA
Ferrero
A
A
Celano
A
A
Fracchioli
S
S
Donadio
M
M
Passera
R
R
Cattel
L
L
Bumma
C
C
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine