Temozolomide in secondary prevention of HER2-positive breast cancer brain metastases

Future Oncol. 2020 May;16(14):899-909. doi: 10.2217/fon-2020-0094. Epub 2020 Apr 9.

Abstract

Brain metastases occur in up to 25-55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates of recurrence or progression, limiting survival and quality of life in most patients. Temozolomide (TMZ) is known to penetrate the blood-brain barrier and is US FDA approved for treatment of glioblastoma. Our group has demonstrated that low doses of TMZ administered in a prophylactic, metronomic fashion can significantly prevent development of brain metastases in murine models of breast cancer. Based on these findings, we initiated a secondary-prevention clinical trial with oral TMZ given to HER2-positive breast cancer patients with brain metastases after recent local treatment in combination with T-DM1 for systemic control of disease. Primary end point is freedom from new brain metastases at 1 year. (NCT03190967).

Keywords: T-DM1; brain metastases; metastatic breast cancer; secondary prevention; temozolomide.

Publication types

  • Clinical Trial Protocol
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Brain Neoplasms / prevention & control*
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Research Design
  • Telomerase / metabolism*
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use*

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • TERT protein, human
  • Telomerase
  • Temozolomide

Associated data

  • ClinicalTrials.gov/NCT03190967