Phase II Trial of Gefitinib in Recurrent Glioblastoma

Main Category: Cancer / Oncology
Article Date: 26 Jan 2004 - 0:00 PDT

email to a friend   printer friendly   opinions  

American Society of Clinical Oncology
http://www.jco.org/cgi/content/abstract/22/1/133

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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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

• Additional
• References
• Citations