Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma

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/ m(2)/ 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% Cl, 17 to 26 weeks), the median survival time from diagnosis of progression was 38 weeks ( 95% Cl, 30 to 46 weeks), and the 1-year survival rate from progression was 23%. O-6-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.