A phase II study of extended low-dose temozolomide in recurrent malignant gliomas

Neuro Oncol. 2002 Jan;4(1):39-43. doi: 10.1093/neuonc/4.1.39.


Temozolomide is an effective agent in the treatment of recurrent malignant gliomas. The standard dosage is 150-200 mg/m2 per day for 5 days in a 28-day cycle. A prior phase I study established a chronic daily temozolomide dose that significantly increased the total dose administered and suggested a superior response rate. In a prospective phase II trial, we treated 35 patients with recurrent malignant gliomas with temozolomide 75 mg/m2 per day for 42 consecutive days in a 70-day cycle. Median age was 55 years (range, 27-73 years) and median Karnofsky performance score was 70 (range, 60-90). Twenty-eight (79%) patients had glioblastoma multiforme, 3 (9%) anaplastic astrocytoma, 2 (6%) anaplastic oligodendroglioma, and 2 (6%) anaplastic oligoastrocytoma. All but one had prior radiotherapy, and 27 had prior chemotherapy. There were 2 partial (anaplastic astrocytoma) and 3 minor (glioblastoma multiforme) radiographic responses; 17 patients had progressive disease at the end of the first cycle. In 55 cycles of temozolomide, there were 8 episodes of asymptomatic drug-related grade 3 toxicity: 6 lymphopenia, 1 neutropenia, and 1 thrombocytopenia. Median progression-free survival and overall survival were 2.5 and 8.7 months (2.3 and 7.7 months in glioblastoma multiforme patients). At 6 months, progression-free survival and overall survival rates were 27% and 67% (19% and 60% in glioblastoma multiforme). Quality of life scores did not change significantly during treatment. We conclude that the extended low-dose schedule of temozolomide is well tolerated in heavily pre-treated patients; however, our results do not support an improved rate of response or survival.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Dacarbazine / administration & dosage*
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Glioma / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prospective Studies
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome


  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide