title: PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer.
abstract: OBJECTIVE
  Vintafolide (EC145) is a folic acid-desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, (99m)Tc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined.
  
  
  METHODS
  Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m(2) intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups.
  
  
  RESULTS
  The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806).
  
  
  CONCLUSIONS
  Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.
authors.affiliation: R. Wendel Naumann and James T. Symanowski, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC; Robert L. Coleman, MD Anderson Cancer Center, University of Texas, Houston; Michael G. Teneriello, Texas Oncology, Austin, TX; Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Edward A. Sausville, Greenebaum Cancer Center, University of Maryland, Baltimore, MD; Elzbieta Kutarska, Centrum Onkologii Ziemi Lubelskiej, Lubland; Elzbieta Nowara, Instytut im. Marii Skłodowskiej-Curie, Gliwice, Poland; Sharad A. Ghamande, Georgia Health Sciences University, Augusta, GA; Nashat Y. Gabrail, Gabrail Cancer Center, Canton, OH; Stephen E. DePasquale, Chattanooga's Program in Women's Oncology, Chattanooga, TN; Lucy Gilbert, McGill University Health Centre, Montreal, Quebec, Canada; Robert H. Gersh, Cancer Care Northwest, Spokane, WA; Wael A. Harb, Horizon Oncology Research, Lafayette; Chandra D. Lovejoy, Christopher P. Leamon, David E. Morgenstern, and Richard A. Messmann, Endocyte, West Lafayette, IN; Panagiotis A. Konstantinopoulos, Beth Israel Deaconess Medical Center; and Richard T. Penson, Dana-Farber Cancer Center, Massachusetts General Hospital, Boston, MA.
authors.forename: R Wendel
authors.initials: RW
authors.lastname: Naumann
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
authors.forename: Edward A
authors.initials: EA
authors.lastname: Sausville
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kutarska
authors.forename: Sharad A
authors.initials: SA
authors.lastname: Ghamande
authors.forename: Nashat Y
authors.initials: NY
authors.lastname: Gabrail
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Depasquale
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Nowara
authors.forename: Lucy
authors.initials: L
authors.lastname: Gilbert
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gersh
authors.forename: Michael G
authors.initials: MG
authors.lastname: Teneriello
authors.forename: Wael A
authors.initials: WA
authors.lastname: Harb
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Konstantinopoulos
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: James T
authors.initials: JT
authors.lastname: Symanowski
authors.forename: Chandra D
authors.initials: CD
authors.lastname: Lovejoy
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Leamon
authors.forename: David E
authors.initials: DE
authors.lastname: Morgenstern
authors.forename: Richard A
authors.initials: RA
authors.lastname: Messmann
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010984:Platinum / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D016896:Treatment Outcome; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C520389:EC145; C473829:EC20 folate peptide; D009842:Oligopeptides; D014748:Vinca Alkaloids; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D010984:Platinum; D004317:Doxorubicin; D005492:Folic Acid