|
|
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@mc.duke.edu. Submitted January 2,
2002; accepted October 22, 2002.
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.
© 2003 American Society for
Clinical Oncology
Source:
http://www.jco.org/cgi/content/abstract/21/4/646
HTML Full Text: http://www.jco.org/cgi/content/full/21/4/646
PDF Full Text: http://www.jco.org/cgi/reprint/21/4/646
|
