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Efficacy and Tolerability of Temozolomide in an Alternating Weekly Regimen in Patients With Recurrent Glioma

Antje Wick, Jörg Felsberg, Joachim P. Steinbach, Ulrich Herrlinger, Michael Platten, Britta Blaschke, Richard Meyermann, Guido Reifenberger, Michael Weller, Wolfgang Wick

From the Department of General Neurology, Hertie Institute for Clinical Brain Research; Department of Neuropathology, University of Tübingen, Tübingen; and the Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany

Address reprint requests to Wolfgang Wick, MD, Department of Neurooncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; e-mail: wolfgang.wick{at}med.uni-heidelberg.de

Purpose: Evaluation of toxicity and efficacy of an alternating weekly regimen of temozolomide administered 1 week on and 1 week off in patients with recurrent glioma.

Patients and Methods: Ninety adult patients with recurrent gliomas accrued in one center received chemotherapy with temozolomide at 150 mg/m²/d (days 1 through 7 and 15 through 21 every 4 weeks) with individual dose adjustments according to hematologic toxicity.

Results: A total of 906 treatment weeks were delivered. Grade 4 hematotoxicity according to the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0) was observed in 24 treatment weeks (2.6%). CTCAE grade 4 lymphopenia eventually developed in 11 patients (12%). There were neither cumulative lymphopenias nor opportunistic infections. The progression-free survival (PFS) rate at 6 months for glioblastoma patients was 43.8%. The median PFS in these patients was 24 weeks (95% CI, 17 to 26 weeks), the median survival time from diagnosis of progression was 38 weeks (95% CI, 30 to 46 weeks), and the 1-year survival rate from progression was 23%. O⁶-methylguanine DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was not associated with longer PFS (log-rank P = .37).

Conclusion: These data imply that the alternating weekly schedule is feasible, safe, and effective and clearly warrants investigation in randomized studies. Compared with more protracted low-dose temozolomide schedules, the 1-week-on/1-week-off schedule may be less toxic. We provide preliminary evidence that this dose-dense schedule is also active in patients with tumors lacking MGMT gene promoter methylation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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