title: Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer.
abstract: OBJECTIVE
  Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients.
  
  
  METHODS
  Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life.
  
  
  RESULTS
  In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia.
  
  
  CONCLUSIONS
  Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.
authors.affiliation: Washington University School of Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, St. Louis, MO 63110, USA. mutchd@msnotes.wustl.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Mauro
authors.initials: M
authors.lastname: Orlando
authors.forename: Tiana
authors.initials: T
authors.lastname: Goss
authors.forename: Michael G
authors.initials: MG
authors.lastname: Teneriello
authors.forename: Alan N
authors.initials: AN
authors.lastname: Gordon
authors.forename: Scott D
authors.initials: SD
authors.lastname: McMeekin
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Scribner
authors.forename: Martin
authors.initials: M
authors.lastname: Marciniack
authors.forename: R Wendel
authors.initials: RW
authors.lastname: Naumann
authors.forename: Angeles Alvarez
authors.initials: AA
authors.lastname: Secord
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002945:Cisplatin; D000093542:Gemcitabine