Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases

Cancer. 2008 Nov 1;113(9):2524-31. doi: 10.1002/cncr.23859.


Background: Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5-day oral schedule every 4 weeks.

Methods: A single-institution phase 2 clinical trial was conducted to determine the efficacy and the safety profile of a new regimen based on a dose-intensified, protracted course of TMZ after whole-brain radiotherapy (WBRT). Patients were eligible if they had at least 1 bidimensionally measurable brain metastasis from breast cancer and nonsmall cell lung cancer (NSCLC). Twenty-seven patients were treated with 30 grays (Gy) of WBRT with concomitant TMZ (75 mg/m(2)/day) for 10 days, and subsequent TMZ at a dose of 75 mg/m(2) per day for 21 days every 4 weeks, for up to 12 cycles.

Results: Two complete responses (7.4%) and 11 partial responses (40.7%) were achieved. The schedule appeared to be well tolerated, with grade 3 toxicity (graded according to National Cancer Institute Common Toxicity Criteria) observed in only 2 patients. The overall median survival was 8.8 months and the median progression-free survival was 6 months.

Conclusions: The concomitant use of WBRT and protracted low-dose TMZ appears to be an active, well-tolerated regimen. The observed antitumor activity suggests the need for further investigation of this schedule in combination with other anticancer agents for the concomitant treatment of brain metastases and primary cancers.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Bone Marrow / drug effects
  • Bone Marrow / radiation effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / therapy*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Combined Modality Therapy
  • Cranial Irradiation*
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Female
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / radiotherapy
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / radiotherapy
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Remission Induction
  • Survival Rate
  • Temozolomide


  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide