Dose-intensity temozolomide after concurrent chemoradiotherapy in operated high-grade gliomas

J Neurooncol. 2008 Dec;90(3):315-9. doi: 10.1007/s11060-008-9663-9. Epub 2008 Aug 8.

Abstract

Purpose: We performed a new phase II trial enrolling patients with newly diagnosed high-grade glioma (HGG) to test the efficacy of a weekly alternating temozolomide (TMZ) schedule after surgery and concomitant chemoradiotherapy.

Methods: From January 2005 to January 2007, 34 patients (21 men, 13 women; age range 30-70, mean age 53) were enrolled. There were 32 glioblastoma multiforme and two anaplastic astrocytoma. Each patient after surgery received standard concurrent chemoradiotherapy. After a 4-week break, patients were then to receive 12 cycles of 1-week-on/1-week-off TMZ, with 75 mg/m(2) for the first cycle, 100 mg/m(2) for the second, 125 mg/m(2) for the third, and 150 mg/m(2) from the fourth to the 12th. Hematological toxicity was monitored every week during concomitant chemoradiotherapy and then every 4 weeks.

Results: After 12 months from the end of radiotherapy, the overall survival (OS) rate was 59% (20/38), distributed as follows: 60% (18/30) for recursive partitioning analysis (RPA) class 4 patients and 33% (1/3) for RPA class 6 patients; the only RPA class 1 patient was alive and disease free at the time of writing. Median OS was 13 months [95% confidence interval (CI) 11.02-14.98 months]. Hematological toxicity was seen in six patients (18%): grade 1 neutropenia in four, grade 2 thrombocytopenia in one, and grade 4 thrombocytopenia plus grade 1 neutropenia in one. There was one case of opportunistic infection (Pneumocystis carinii pneumonitis).

Conclusion: The toxicity of the TMZ dose-dense regimen was very low. Results seem to be encouraging for RPA lower classes (patients with good prognostic factors).

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / classification
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Glioma / classification
  • Glioma / drug therapy*
  • Glioma / mortality
  • Glioma / radiotherapy
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Retrospective Studies
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide