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

• DOI: 10.1200/jco.2011.29.15_suppl.2038
• Publication Date: 2017-02-23T18:58:03Z
• Authors: S. Hammond; A. D. Norden; G. J. Lesser; J. Drappatz; C. E. Fadul; T. Batchelor; E. C. Quant; R. Beroukhim; A. Muzikansky; A. S. Ciampa; L. M. Doherty; D. C. LaFrankie; S. Ruland; C. A. Bochacki; K. Griffin; M. Gerard; C. Sceppa; M. R. Rosenfeld; P. Y. Wen
• Keywords: Temozolomide; Clinical endpoint; Progression-free survival; O-6-methylguanine-DNA methyltransferase

2038 Background: Most GBM patients relapse within 1 year from diagnosis. Among who progress on standard temozolomide, the optimal therapy is unknown. Resistance to temozolomide partially mediated by DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT may be depleted prolonged administration, dose-intense schedules overcome resistance in with recurrent GBM. Methods: This a phase 2 single arm study of 75-100 mg/m2/day for 21 days each 28-day cycle. Patients have first recurrence following therapy, including at least cycles adjuvant temozolomide. The primary endpoint 6-month progression-free survival (PFS6). Results: Forty-eight participants been accrued, one whom withdrew prior treatment. There are 26 men (55%), median age 57 (range 25-74), KPS 90 60-100). Of 40 methylation results, 7 methylated (17.5%). were 6 (13%) partial responses (PR). Eighteen (38%) achieved stable disease (SD). Median PFS was 10 weeks (95% CI: 8-17) and PFS6 23%. OS 13 months 8-not reached). had 7.4 CI 1.9-15.6), unmethylated promoters 1.9-3.8; p=0.08). 16 16-not yet reached), 11.5 reached; p=0.05). probability achieving PR/SD higher (p=0.03). Response, PFS, did not depend number or time off Treatment well tolerated limited Grade 3 neutropenia (n=3) thrombocytopenia (n=4). Conclusions: Dose-intense 21/28 day schedule safe regimen recurrence. Updated efficacy results will presented.