title: Decreased hypersensitivity reactions with carboplatin-pegylated liposomal doxorubicin compared to carboplatin-paclitaxel combination: analysis from the GCIG CALYPSO relapsing ovarian cancer trial.
abstract: OBJECTIVE
  To describe and analyze observed hypersensitivity reactions (HSR) from the randomized, multicenter phase III CALYPSO trial that evaluated the efficacy and safety of the combination of carboplatin and pegylated liposomal doxorubicin (CD) compared with standard carboplatin-paclitaxel (CP) in patients with platinum-sensitive relapsed ovarian cancer (ROC).
  
  
  METHODS
  HSR documented within case report forms and SAE reports were specifically analyzed. Analyses were based on the population with allergy of any grade and for grade >2 allergy.
  
  
  RESULTS
  Overall 976 patients were recruited to this phase III trial, with toxicity data available for 466 and 502 on the CD and CP arms, respectively. There was a 15.5% HSR rate associated with CD (2.4% grade >2) versus 33.1% with CP (8.8% grade >2), p<0.001. HSRs occurred more often during first cycle in the CD (46%) arm than in the CP arm (16%). Multivariate predictors of allergy were chemotherapy regimen and age; patients randomized to CD and patients ≥ 70 years old on CP had less allergy. Few patients (<6%) stopped treatment due to allergy. Allergy rates were higher in patients who did not receive prior supportive treatment; however there was no relationship between allergy and the type of carboplatin product received, or response rate.
  
  
  CONCLUSIONS
  Use of PLD with carboplatin instead of paclitaxel and older age were the only 2 factors predicting a low rate of HSRs in patients with ROC. CD has previously demonstrated superior progression-free survival and therapeutic index than CP. Taken together these data support the use of CD as a safe and effective therapeutic option for platinum-sensitive ROC.
authors.affiliation: Centre François Baclesse, Medical Oncology Department, Caen, France. f.joly@baclesse.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Michel
authors.initials: M
authors.lastname: Fabbro
authors.forename: Mark
authors.initials: M
authors.lastname: Donoghoe
authors.forename: Karin
authors.initials: K
authors.lastname: Boman
authors.forename: Akira
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Michelle
authors.initials: M
authors.lastname: Vaughan
authors.forename: Alexander
authors.initials: A
authors.lastname: Reinthaller
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.forename: Tiziana
authors.initials: T
authors.lastname: Dell'Anna
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel