title: A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas: a report from the Pediatric Brain Tumor Consortium.
abstract: This phase II study was designed to assess the safety and efficacy of gefitinib given with and following radiation therapy in children newly diagnosed with a poor prognosis brainstem glioma. Eligible patients were those with a previously untreated nondisseminated diffuse intrinsic brainstem glioma. Histological confirmation was not required, provided patients had a characteristic clinical history and MRI findings. Treatment consisted of gefitinib, administered orally, 250 mg/m(2)/day, during standard external beam radiotherapy, continuing for up to 13 monthly courses in the absence of disease progression or unacceptable toxicity. Toxicities, particularly intratumoral hemorrhage, were monitored. Pharmacokinetics and investigational imaging studies were performed in consenting patients. Forty-three eligible patients were included in the study. Therapy was well tolerated; only 4 patients were withdrawn from the study for dose-limiting toxicity after receiving therapy for 6, 9, 17, and 24 weeks. The 12- and 24-month progression-free survival rates were 20.9 ±5.6 % and 9.3 ±4%, respectively. Overall survival rates were 56.4 ±7.6% and 19.6 ±5.9%, respectively, which appear nominally superior to other contemporaneous Pediatric Brain Tumor Consortium trials. Three patients remain progression-free survivors with ≥36 months follow-up. The observation that a subset of children with this generally fatal tumor experienced long-term progression-free survival, coupled with recent observations regarding the molecular features of brainstem gliomas, raises the possibility that prospective molecular characterization may allow enrichment of treatment responders and improvement in outcome results in future studies of biologically targeted agents.
authors.affiliation: Department of Neurosurgery, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. pollackif@upmc.edu
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Tina Young
authors.initials: TY
authors.lastname: Poussaint
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Anu
authors.initials: A
authors.lastname: Banerjee
authors.forename: James G
authors.initials: JG
authors.lastname: Douglas
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: J Russell
authors.initials: JR
authors.lastname: Geyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D005260:Female; D000077156:Gefitinib; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib