title: Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: results from a prospectively designed analysis of progression-free survival.
abstract: OBJECTIVE
  Interferon gamma (IFN-gamma) is a pleiotropic cytokine with antiproliferative, immunostimulatory, and chemosensitization properties. This trial was designed to evaluate IFN-gamma 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer (OC) and primary peritoneal carcinoma (PPC) patients.
  
  
  METHODS
  Eligible patients were randomized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-gamma 1b (100 microg 3x/wk subcutaneously). The primary endpoint was overall survival (OS) time (target hazard ratio (HR)=0.77). Secondary endpoints included progression-free survival (target HR=0.7), based on blinded review of serial imaging scans, physical exams, and CA-125 levels.
  
  
  RESULTS
  847 patients were enrolled (OC 774, PPC 73) in Europe (n=539) and North/South America (n=308) from January 29, 2002 to March 31, 2004 and stratified according to: optimal debulking (n=271) versus suboptimal debulking with plans for interval debulking (PID) (n=238) or no PID (n=338). The study stopped early following a protocol-defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-gamma 1b plus chemotherapy compared to chemotherapy alone (1138 days vs. not estimable, HR=1.45, 95% CI=1.15-1.83). At the time of the analysis, 169 of 426 (39.7%) patients in the IFN-gamma 1b plus chemotherapy group had died compared to 128 of 421 (30.4%) in the chemotherapy alone group. Serious adverse events were more common in the IFN-gamma 1b plus chemotherapy group (48.5% vs. 35.4%), primarily due to a higher incidence of serious hematological toxicities (34.5% vs. 22.7%).
  
  
  CONCLUSIONS
  Treatment with IFN-gamma 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer.
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, AZ, USA. dalberts@azcc.arizona.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
authors.forename: Gary
authors.initials: G
authors.lastname: Johnson
authors.forename: Mariusz
authors.initials: M
authors.lastname: Bidzinski
authors.forename: David R
authors.initials: DR
authors.lastname: Kardatzke
authors.forename: Williamson Z
authors.initials: WZ
authors.lastname: Bradford
authors.forename: Jeff
authors.initials: J
authors.lastname: Loutit
authors.forename: David H
authors.initials: DH
authors.lastname: Kirn
authors.forename: Mary C
authors.initials: MC
authors.lastname: Clouser
authors.forename: Maurie
authors.initials: M
authors.lastname: Markman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000503:physiopathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016190:Carboplatin; D017239:Paclitaxel