Related Experiment Video
Updated: May 12, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase 2 study of dose-intense temozolomide in recurrent glioblastoma
Andrew D Norden1, Glenn J Lesser, Jan Drappatz
1Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, 450 Brookline Ave., Boston, MA 02215, USA.
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.
