Journal of Clinical Oncology, Vol 21, Issue 4
(February), 2003: 646-651
© 2003 American Society for Clinical Oncology
Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma
Jennifer A. Quinn,
David A. Reardon,
Allan H. Friedman,
Jeremy N. Rich,
John H. Sampson,
James M. Provenzale,
Roger E. McLendon,
Sridharan Gururangan,
Darell D. Bigner,
James E. Herndon, II,
Nicholas Avgeropoulos,
Jonathan Finlay,
Sandra Tourt-Uhlig,
Mary Lou Affronti,
Brandon Evans,
Valerie Stafford-Fox,
Sara Zaknoen,
Henry S. Friedman
From the Departments of Surgery, Radiology, Pathology, Biostatistics and Bioinformatics (JH), Duke University Medical Center, Durham, NC; Hassenfeld Cancer Center, and Beth Israel Medical Center, New York, NY; Walt Disney Memorial Cancer Institute, Orlando, FL; and Schering-Plough Research Institute, Kenilworth, NJ.
Address reprint requests to Jennifer A. Quinn, MD, The Brain Tumor Center at Duke, Box 3624 Duke University Medical Center, Durham, NC 27710; email: quinn008{at}mc.duke.edu.
Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma.
Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity.
Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to  months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced  grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death.
Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.
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