title: Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial.
abstract: BACKGROUND
  Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1.
  
  
  METHODS
  Eligible patients had to be aged 3-65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m(2) twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009.
  
  
  RESULTS
  Six of 36 patients (17%, 95% CI 6-33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one).
  
  
  CONCLUSIONS
  Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results.
  
  
  BACKGROUND
  Novartis Pharmaceuticals, the Indiana University Simon Cancer Centre, and the Indiana University Herman B Wells Center for Pediatric Research.
authors.affiliation: Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, USA. krobert@iupui.edu
authors.forename: Kent A
authors.initials: KA
authors.lastname: Robertson
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Nalepa
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Yang
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bowers
authors.forename: Chang Y
authors.initials: CY
authors.lastname: Ho
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.forename: James M
authors.initials: JM
authors.lastname: Croop
authors.forename: Terry A
authors.initials: TA
authors.lastname: Vik
authors.forename: Scott C
authors.initials: SC
authors.lastname: Denne
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Hingtgen
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Walsh
authors.forename: Menggang
authors.initials: M
authors.lastname: Yu
authors.forename: Kamnesh R
authors.initials: KR
authors.lastname: Pradhan
authors.forename: Mary K
authors.initials: MK
authors.lastname: Edwards-Brown
authors.forename: Mervyn D
authors.initials: MD
authors.lastname: Cohen
authors.forename: James W
authors.initials: JW
authors.lastname: Fletcher
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Travers
authors.forename: Karl W
authors.initials: KW
authors.lastname: Staser
authors.forename: Melissa W
authors.initials: MW
authors.lastname: Lee
authors.forename: Marcie R
authors.initials: MR
authors.lastname: Sherman
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Davis
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Miller
authors.forename: David A
authors.initials: DA
authors.lastname: Ingram
authors.forename: D Wade
authors.initials: DW
authors.lastname: Clapp
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018318:Neurofibroma, Plexiform / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000150:complications*; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate