title: Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup.
abstract: OBJECTIVE
  To determine if incorporation of an additional cytotoxic agent improves overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma who receive carboplatin and paclitaxel.
  
  
  METHODS
  Women with stages III to IV disease were stratified by coordinating center, maximal diameter of residual tumor, and intent for interval cytoreduction and were then randomly assigned among five arms that incorporated gemcitabine, methoxypolyethylene glycosylated liposomal doxorubicin, or topotecan compared with carboplatin and paclitaxel. The primary end point was OS and was determined by pairwise comparison to the reference arm, with a 90% chance of detecting a true hazard ratio of 1.33 that limited type I error to 5% (two-tail) for the four comparisons.
  
  
  RESULTS
  Accrual exceeded 1,200 patients per year. An event-triggered interim analysis occurred after 272 events on the reference arm, and the study closed with 4,312 women enrolled. Arms were well balanced for demographic and prognostic factors, and 79% of patients completed eight cycles of therapy. There were no improvements in either PFS or OS associated with any experimental regimen. Survival analyses of groups defined by size of residual disease also failed to show experimental benefit in any subgroup.
  
  
  CONCLUSIONS
  Compared with standard paclitaxel and carboplatin, addition of a third cytotoxic agent provided no benefit in PFS or OS after optimal or suboptimal cytoreduction. Dual-stage, multiarm, phase III trials can efficiently evaluate multiple experimental regimens against a single reference arm. The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes for women with advanced EOC.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111, USA. michael.bookman@fccc.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
authors.forename: Mark F
authors.initials: MF
authors.lastname: Brady
authors.forename: William P
authors.initials: WP
authors.lastname: McGuire
authors.forename: Peter G
authors.initials: PG
authors.lastname: Harper
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Fowler
authors.forename: Peter A
authors.initials: PA
authors.lastname: Argenta
authors.forename: Koen
authors.initials: K
authors.lastname: De Geest
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Swart
authors.forename: Edward L
authors.initials: EL
authors.lastname: Trimble
authors.forename: Chrisann
authors.initials: C
authors.lastname: Accario-Winslow
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Roth
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine