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Phase II Trial
of Gefitinib in Recurrent Glioblastoma
Jeremy N. Rich, David
A. Reardon, Terry Peery, Jeannette M. Dowell, Jennifer
A. Quinn, Kara L. Penne, Carol J. Wikstrand, Lauren
B. Van Duyn, Janet E. Dancey, Roger E. McLendon,
James C. Kao, Timothy T. Stenzel, B.K. Ahmed
Rasheed, Sandra E. Tourt-Uhlig, James E. Herndon, II,
James J. Vredenburgh, John H. Sampson, Allan H.
Friedman, Darell D. Bigner, Henry S. Friedman
From the Departments of Medicine,
Surgery, Pathology, and Cancer Center Biostatistics, Duke University Medical
Center, Durham, NC; and the National Cancer Institute, Bethesda, MD.
Address reprint requests to Jeremy N. Rich, MD, Duke University Medical Center,
Box 2900, Durham, NC 27710; e-mail: rich0001@mc.duke.edu
Purpose. To evaluate the efficacy and
tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington,
DE), a novel epidermal growth factor receptor tyrosine kinase
inhibitor, in patients with recurrent glioblastoma.
Patients and Methods. This was an
open-label, single-center phase II trial.
Fifty-seven patients with first recurrence of a glioblastoma who were
previously treated with surgical resection, radiation, and usually
chemotherapy underwent an open biopsy or resection at evaluation for
confirmation of tumor recurrence.
Each patient initially received 500 mg of gefitinib orally once
daily; dose escalation to 750 mg then 1,000 mg, if a patient received
enzyme-inducing antiepileptic drugs or dexamethasone, was allowed
within each patient.
Results. Although no objective tumor
responses were seen among the 53 assessable patients, only 21% of
patients (11 of 53 patients) had measurable disease at treatment
initiation.
Seventeen percent of patients (nine of 53 patients) underwent at
least six 4-week cycles, and the 6-month event-free survival (EFS)
was 13% (seven of 53 patients).
The median EFS time was 8.1 weeks, and the median overall survival
(OS) time from treatment initiation was 39.4 weeks.
Adverse events were generally mild (grade 1 or 2) and consisted
mainly of skin reactions and diarrhea.
Drug-related toxicities were more frequent at higher doses.
Withdrawal caused by drug-related adverse events occurred in 6% of
patients (three of 53 patients).
Although the presence of diarrhea positively predicted favorable OS
from treatment initiation, epidermal growth factor receptor
expression did not correlate with either EFS or OS.
Conclusion. Gefitinib is well tolerated
and has activity in patients with recurrent glioblastoma.
Further study of this agent at higher doses is warranted.
Supported by Federal funds from the
National Cancer Institute, National Institutes of Health, Bethesda,
MD (grant No. R21 CA91548), and foundation funds from Accelerate
Brain Cancer Cure.
Presented in part at the 39th Annual Meeting of the American Society
of Clinical Oncology, May 31–June 3, 2003, Chicago, IL.
© 2004 American Society for Clinical
Oncology
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