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

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).

• Authors: Alexandra S Zimmer, Seth M Steinberg, Dee Dee Smart, Mark R Gilbert, Terri S Armstrong, Eric Burton, Nicole Houston, Nadia Biassou, Brunilde Gril, Priscilla K Brastianos, Scott Carter, David Lyden, Stanley Lipkowitz, Patricia S Steeg
• Journal: Future oncology (London, England) (Future Oncol) Vol. 16 Issue 14 Pg. 899-909 (May 2020) ISSN: 1744-8301 [Electronic] England
• PMID: 32270710 (Publication Type: Clinical Trial Protocol, Journal Article)

Chemical References

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

Topics

• Animals
• Female
• Humans
• Antineoplastic Agents, Alkylating (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers, Tumor
• Brain Neoplasms (secondary, therapy)
• Breast Neoplasms (metabolism, pathology, therapy)
• Drug Evaluation, Preclinical
• Research Design
• Telomerase (metabolism)
• Temozolomide (pharmacology, therapeutic use)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic