RTOG 0211: a phase 1/2 study of radiation therapy with concurrent gefitinib for newly diagnosed glioblastoma patients. Int J Radiat Oncol Biol Phys 2013 Apr 01;85(5):1206-11
Date
11/28/2012Pubmed ID
23182702Pubmed Central ID
PMC4199329DOI
10.1016/j.ijrobp.2012.10.008Scopus ID
2-s2.0-84875239034 (requires institutional sign-in at Scopus site) 119 CitationsAbstract
PURPOSE: 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 AND MATERIALS: 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.
Author List
Chakravarti A, Wang M, Robins HI, Lautenschlaeger T, Curran WJ, Brachman DG, Schultz CJ, Choucair A, Dolled-Filhart M, Christiansen J, Gustavson M, Molinaro A, Mischel P, Dicker AP, Bredel M, Mehta MAuthor
Christopher J. Schultz MD Chair, Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Age FactorsAntineoplastic Agents
Biomarkers, Tumor
Brain Neoplasms
Combined Modality Therapy
ErbB Receptors
Glioblastoma
Humans
Maximum Tolerated Dose
Middle Aged
Quinazolines
Radiotherapy Dosage
