title: Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: final survival results of a SWOG (S0200) phase 3 randomized trial.
abstract: OBJECTIVE
  Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent.
  
  
  METHODS
  To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m(2)) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed.
  
  
  RESULTS
  In the limited number of patients (n=61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p=0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p=0.0008), with 5 being >grade 2 in severity.
  
  
  CONCLUSIONS
  Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions.
authors.affiliation: University of Texas, M.D. Anderson Cancer Center, Unit 1435, Houston, TX 77030, USA. mmarkman@mdanderson.org
authors.forename: Maurie
authors.initials: M
authors.lastname: Markman
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Sharon
authors.initials: S
authors.lastname: Wilczynski
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Lopez
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: David P
authors.initials: DP
authors.lastname: Michelin
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Lanzotti
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin