TY - JOUR
T1 - Phase II evaluation of gefitinib in patients with newly diagnosed grade 4 astrocytoma
T2 - Mayo/north central cancer treatment group study n0074
AU - Uhm, Joon H.
AU - Ballman, Karla V.
AU - Wu, Wenting
AU - Giannini, Caterina
AU - Krauss, J. C.
AU - Buckner, Jan C.
AU - James, C. D.
AU - Scheithauer, Bernd W.
AU - Behrens, Robert J.
AU - Flynn, Patrick J.
AU - Schaefer, Paul L.
AU - Dakhill, Shaker R.
AU - Jaeckle, Kurt A.
N1 - Funding Information:
This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants: CA-25224 , CA-37404 , CA-35195 , CA-35101 , CA-37417 , CA-63849 , CA-35113 , CA-35267 , CA-35269 , CA-35103 , CA-63848 , CA-35415 , CA-35431 , CA-52352 , and CA-35448 from the National Cancer Institute, Department of Health and Human Services. We acknowledge the support of AstraZeneca for this study.
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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.
AB - 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.
KW - Astrocytoma
KW - EGFR
KW - Glioblastoma
KW - Glioma
UR - http://www.scopus.com/inward/record.url?scp=79955582712&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955582712&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2010.01.070
DO - 10.1016/j.ijrobp.2010.01.070
M3 - Article
C2 - 20510539
AN - SCOPUS:79955582712
SN - 0360-3016
VL - 80
SP - 347
EP - 353
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -