title: Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme.
abstract: OBJECTIVE
  Cilengitide, an inhibitor of alphavbeta3 and alphavbeta5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence.
  
  
  METHODS
  Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments.
  
  
  RESULTS
  Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months.
  
  
  CONCLUSIONS
  Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. reard003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Karen L
authors.initials: KL
authors.lastname: Fink
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Alison
authors.initials: A
authors.lastname: O'Neill
authors.forename: Scott
authors.initials: S
authors.lastname: Plotkin
authors.forename: Michael
authors.initials: M
authors.lastname: Glantz
authors.forename: Paula
authors.initials: P
authors.lastname: Ravin
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: Keith M
authors.initials: KM
authors.lastname: Rich
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: William R
authors.initials: WR
authors.lastname: Shapiro
authors.forename: Susan
authors.initials: S
authors.lastname: Burdette-Radoux
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dropcho
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Wittemer
authors.forename: Johannes
authors.initials: J
authors.lastname: Nippgen
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.forename: L Burt
authors.initials: LB
authors.lastname: Nabors
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors*; D011788:Quality of Life; D012910:Snake Venoms / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D012910:Snake Venoms; C507169:cyclic arginine-glycine-aspartic acid peptide; C422910:Cilengitide