title: Phase II study of cilengitide in the treatment of refractory or relapsed high-grade gliomas in children: a report from the Children's Oncology Group.
abstract: BACKGROUND
  Cilengitide, an αv integrin antagonist, has demonstrated activity in recurrent adult glioblastoma (GBM). The Children's Oncology Group ACNS0621 study thus evaluated whether cilengitide is active as a single agent in the treatment of children with refractory high-grade glioma (HGG). Secondary objectives were to investigate the pharmacokinetics and pharmacogenomics of cilengitide in this population.
  
  
  METHODS
  Cilengitide (1800 mg/m(2)/dose intravenous) was administered twice weekly until evidence of disease progression or unacceptable toxicity. Thirty patients (age range, 1.1-20.3 years) were enrolled, of whom 24 were evaluable for the primary response end point.
  
  
  RESULTS
  Toxicity was infrequent and mild, with the exception of one episode of grade 2 pain possibly related to cilengitide. Two intratumoral hemorrhages were reported, but only one (grade 2) was deemed to be possibly related to cilengitide and was in the context of disease progression. One patient with GBM received cilengitide for 20 months and remains alive with continuous stable disease. There were no other responders, with median time to tumor progression of 28 days (range, 11-114 days). Twenty-one of the 24 evaluable patients died, with a median time from enrollment to death of 172 days (range, 28-325 days). The 3 patients alive at the time of this report had a follow-up time of 37, 223, and 1068 days, respectively.
  
  
  CONCLUSIONS
  We conclude that cilengitide is not effective as a single agent for refractory pediatric HGG. However, further study evaluating combination therapy with cilengitide is warranted before a role for cilengitide in the treatment of pediatric HGG can be excluded.
authors.affiliation: Corresponding Author: Tobey J. MacDonald, MD, Emory Children's Center, Aflac Cancer and Blood Disorders Center, 2015 Uppergate Drive NE, Suite 442, Atlanta, GA 30322. tobey.macdonald@emory.edu.
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vezina
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: David
authors.initials: D
authors.lastname: Turner
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Pierson
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D016879:Salvage Therapy; D012910:Snake Venoms / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015996:Survival Rate; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D012910:Snake Venoms; C422910:Cilengitide
keywords: childhood; cilengitide; high-grade glioma