title: Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas.
abstract: BACKGROUND
  Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG). Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy (RT) in children with newly diagnosed HGG.
  
  
  METHODS
  Following maximum surgical resection, patients between 3 and 21 years with non-metastatic HGG received local RT at 59.4 Gy (54 Gy for spinal tumors and those with ≥70% brain involvement). Erlotinib started on day 1 of RT (120 mg/m(2) per day) and continued for 2 years unless there was tumor progression or intolerable toxicities. The 2-year progression-free survival (PFS) was estimated for patients with intracranial anaplastic astrocytoma (AA) and glioblastoma (GBM).
  
  
  RESULTS
  Median age at diagnosis for 41 patients with intracranial tumors (21 with GBM and 20 with AA) was 10.9 years (range, 3.3-19 years). The 2-year PFS for patients with AA and GBM was 15 ± 7 and 19 ± 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n = 11), dermatologic (n = 5), and metabolic (n = 4). One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis.
  
  
  CONCLUSIONS
  Although therapy with erlotinib was mostly well-tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and GBM.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital , Memphis, TN , USA ; Department of Pediatrics, University of Tennessee Health Sciences Center , Memphis, TN , USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Qaddoumi
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: Atmaram S
authors.initials: AS
authors.lastname: Pai Panandiker
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital , Memphis, TN , USA ; Department of Pediatrics, University of Tennessee Health Sciences Center , Memphis, TN , USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wetmore
authors.affiliation: Department of Neurosciences, University of California San Diego , San Diego, CA , USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Crawford
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.affiliation: Semmes-Murphey Neurologic and Spine Institute , Memphis, TN , USA.
authors.forename: Fredrick A
authors.initials: FA
authors.lastname: Boop
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital , Memphis, TN , USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital , Memphis, TN , USA ; Department of Pediatrics, University of Tennessee Health Sciences Center , Memphis, TN , USA.
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital , Memphis, TN , USA ; Department of Pediatrics, University of Tennessee Health Sciences Center , Memphis, TN , USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
keywords: epidermal growth factor receptor; erlotinib; high-grade glioma; pediatric; phase II; radiotherapy
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