title: Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Via Ventimiglia 3, 10126 Turin, Italy. dhocc@libero.it
authors.forename: D
authors.initials: D
authors.lastname: Katsaros
authors.forename: M V
authors.initials: MV
authors.lastname: Oletti
authors.forename: I A
authors.initials: IA
authors.lastname: Rigault de la Longrais
authors.forename: A
authors.initials: A
authors.lastname: Ferrero
authors.forename: A
authors.initials: A
authors.lastname: Celano
authors.forename: S
authors.initials: S
authors.lastname: Fracchioli
authors.forename: M
authors.initials: M
authors.lastname: Donadio
authors.forename: R
authors.initials: R
authors.lastname: Passera
authors.forename: L
authors.initials: L
authors.lastname: Cattel
authors.forename: C
authors.initials: C
authors.lastname: Bumma
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine