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

J Clin Oncol. 2007 Aug 1;25(22):3357-61. doi: 10.1200/JCO.2007.10.7722.

Abstract

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% 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%. 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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / adverse effects
  • Brain Neoplasms / drug therapy*
  • DNA Methylation
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Glioma / drug therapy*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Polymerase Chain Reaction
  • Prospective Studies
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide