title: Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.
abstract: OBJECTIVE
  This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).
  
  
  METHODS
  Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.
  
  
  RESULTS
  Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.
  
  
  CONCLUSIONS
  To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
authors.affiliation: University Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel Dieu, Paris, France. epujade@arcagy.org
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: Uwe
authors.initials: U
authors.lastname: Wagner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aavall-Lundqvist
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.forename: Mark
authors.initials: M
authors.lastname: Heywood
authors.forename: Paul A
authors.initials: PA
authors.lastname: Vasey
authors.forename: Birgit
authors.initials: B
authors.lastname: Volgger
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ferrero
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Fur
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D010984:Platinum / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012008:Recurrence
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D010984:Platinum; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel