title: RTOG 0211: a phase 1/2 study of radiation therapy with concurrent gefitinib for newly diagnosed glioblastoma patients.
abstract: OBJECTIVE
  To determine the safety and efficacy of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with radiation for newly diagnosed glioblastoma (GBM) patients.
  
  
  METHODS
  Between March 21, 2002, and May 3, 2004, Radiation Therapy Oncology Group (RTOG) 0211 enrolled 31 and 147 GBM patients in the phase 1 and 2 arms, respectively. Treatment consisted of daily oral gefinitnib started at the time of conventional cranial radiation therapy (RT) and continued post RT for 18 months or until progression. Tissue microarrays from 68 cases were analyzed for EGFR expression.
  
  
  RESULTS
  The maximum tolerated dose (MTD) of gefitinib was determined to be 500 mg in patients on non-enzyme-inducing anticonvulsant drugs (non-EIAEDs). All patients in the phase 2 component were treated at a gefitinib dose of 500 mg; patients receiving EIADSs could be escalated to 750 mg. The most common side effects of gefitinib in combination with radiation were dermatologic and gastrointestinal. Median survival was 11.5 months for patients treated per protocol. There was no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone, matched by RTOG recursive partitioning analysis (RPA) class distribution. Younger age was significantly associated with better outcome. Per protocol stratification, EGFR expression was not found to be of prognostic value for gefitinib + RT-treated patients.
  
  
  CONCLUSIONS
  The addition of gefitinib to RT is well tolerated. Median survival of RTOG 0211 patients treated with RT with concurrent and adjuvant gefitinib was similar to that in a historical control cohort treated with radiation alone.
authors.affiliation: Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University, Columbus, Ohio, USA. Arnab.chakravarti@osumc.edu
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Meihua
authors.initials: M
authors.lastname: Wang
authors.forename: H Ian
authors.initials: HI
authors.lastname: Robins
authors.forename: Tim
authors.initials: T
authors.lastname: Lautenschlaeger
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.forename: David G
authors.initials: DG
authors.lastname: Brachman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schultz
authors.forename: Ali
authors.initials: A
authors.lastname: Choucair
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolled-Filhart
authors.forename: Jason
authors.initials: J
authors.lastname: Christiansen
authors.forename: Mark
authors.initials: M
authors.lastname: Gustavson
authors.forename: Annette
authors.initials: A
authors.lastname: Molinaro
authors.forename: Paul
authors.initials: P
authors.lastname: Mischel
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.forename: Markus
authors.initials: M
authors.lastname: Bredel
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
mesh_terms: D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D066246:ErbB Receptors / Q000378:metabolism; D000077156:Gefitinib; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib