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Clin Cancer Res. 2009 Jan 1;15(1):330-7. doi: 10.1158/1078-0432.CCR-08-0888.

Phase II study of protracted daily temozolomide for low-grade gliomas in adults.

Author information

  • 1Dana-Farber/Brigham and Women's Cancer Center, Center for Neuro-Oncology, Boston, MA 02115, USA.

Abstract

PURPOSE:

Resistance to temozolomide chemotherapy is partly mediated by O(6)-methylguanine-DNA methlytransferase (MGMT). Protracted treatment with temozolomide potentially overcomes MGMT resistance and improves outcome. We conducted a phase II study of protracted daily temozolomide in adults with low-grade gliomas.

EXPERIMENTAL DESIGN:

Patients with newly diagnosed oligodendroglioma or oligoastrocytoma with a MIB-1 index of >5% or recurrent low-grade gliomas received temozolomide (75 mg/m(2)/day in 11-week cycles of 7 weeks on/4 weeks off). Treatment continued for a total of six cycles or until tumor progression or unacceptable toxicity. Primary end point was best overall response rate; secondary end points were progression-free survival, overall survival, and toxicity. We correlated response with MGMT promoter methylation and chromosome 1p/19q deletion status.

RESULTS:

Forty-four patients were treated (14 female, 30 male) with a median follow-up of 39.4 months. Median age was 43 years (range, 20-68 years) and median Karnofsky performance status was 90 (range, 70-100). The regimen was well tolerated. No patients had a complete response (0%), 9 had partial response (20%), 33 had stable disease (75%), and 2 had progressive disease (5%). A total of 21 patients eventually progressed with an overall median progression-free survival of 38 months. Patients with methylated MGMT promoter had a longer overall survival (P = 0.008). Deletion of either 1p or 19q chromosomes also predicted longer overall survival (hazard ratio, 0.17; 95% confidence interval, 0.03-0.93; log-rank P = 0.02).

CONCLUSIONS:

A protracted course of daily temozolomide is a well-tolerated regimen and seems to produce effective tumor control. This compares favorably with historical data on the standard 5-day temozolomide regimen.

PMID:
19118062
[PubMed - indexed for MEDLINE]
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