PURPOSE: Amplification of the epidermal growth factor receptor (EGFR) gene 
represents one of the most frequent gene alterations in glioblastoma (GBM). In 
the current study, we evaluated gefitinib, a potent EGFR inhibitor, in the 
treatment of adults with newly diagnosed GBM.
METHODS AND MATERIALS: Ninety-eight patients (96 evaluable) were accrued between 
May 18, 2001, and August 2, 2002. All were newly diagnosed GBM patients who were 
clinically and radiographically stable/improved after radiation treatment 
(enrollment within 5 weeks of radiation completion). No prior chemotherapy was 
permitted. EGFR amplification/mutation, as assessed by fluorescence in situ 
hybridization and immunohistochemistry, was not required for treatment with 
gefitinib but was studied when tissues were available. Gefitinib was 
administered at 500 mg each day; for patients receiving dexamethasone or 
enzyme-inducing (CYP3A4) agents, dose was escalated to a maximum of 1,000 mg QD. 
Treatment cycles were repeated at 4-week intervals with brain magnetic resonance 
imaging at 8-week intervals.
RESULTS: Overall survival (OS; calculated from time of initial surgery) at 1 
year (primary end point) with gefitinib was 54.2%, which was not statistically 
different compared with that of historical control population (48.9%, data from 
three previous Phase III North Central Cancer Treatment Group studies of newly 
diagnosed GBM patients). Progression-free survival (PFS) at 1 year post-RT 
(16.7%) was also not significantly different to that of historical controls 
(30.3%). Clinical outcome was not affected by EGFR status (amplification or vIII 
mutation). Fatigue (41%), rash (62%), and loose stools (58%) constituted the 
most frequent adverse events, the majority of these being limited to Grade 1/2. 
Of note, the occurrence of drug-related adverse effects, such as loose stools 
was associated with improved OS.
CONCLUSIONS: In our evaluation of nearly 100 patients with newly diagnosed GBM, 
treatment with adjuvant gefitinib post-radiation was not associated with 
significant improvement in OS or PFS. However, patients who experienced 
gefitinib-associated adverse effects (rash/diarrhea) did demonstrate improved 
OS.