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Neuro Oncol. 2013 Jul;15(7):930-5. doi: 10.1093/neuonc/not040. Epub 2013 Apr 3.

Phase 2 study of dose-intense temozolomide in recurrent glioblastoma.

Author information

1
Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, 450 Brookline Ave., Boston, MA 02215, USA.

Abstract

BACKGROUND:

Among patients with glioblastoma (GBM) who progress on standard temozolomide, the optimal therapy is unknown. Resistance to temozolomide is partially mediated by O(6)-methylguanine-DNA methyltransferase (MGMT). Because MGMT may be depleted by prolonged temozolomide administration, dose-intense schedules may overcome resistance.

METHODS:

This was a multicenter, phase 2, single-arm study of temozolomide (75-100 mg/m(2)/day) for 21 days of each 28-day cycle. Patients had GBM in first recurrence after standard therapy. The primary end point was 6-month progression-free survival (PFS6).

RESULTS:

Fifty-eight participants were accrued, 3 of whom were ineligible for analysis; one withdrew before response assessment. There were 33 men (61%), with a median age of 57 years (range, 25-79 years) and a median Karnofsky performance score of 90 (range, 60-100). Of 47 patients with MGMT methylation results, 36 (65%) had methylated tumors. There were 7 (13%) partial responses, and PFS6 was only 11%. Response and PFS did not depend on MGMT status; MSH2, MLH1, or ERCC1 expression; the number of prior temozolomide cycles; or the time off temozolomide. Treatment was well tolerated, with limited grade 3 neutropenia (n = 2) or thrombocytopenia (n = 2).

CONCLUSIONS:

Dose-intense temozolomide on this schedule is safe in recurrent GBM. However, efficacy is marginal and predictive biomarkers are needed.

KEYWORDS:

MGMT promoter methylation; dose-intense temozolomide; recurrent glioblastoma

PMID:
23553268
PMCID:
PMC3688016
DOI:
10.1093/neuonc/not040
[Indexed for MEDLINE]
Free PMC Article
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