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Clinical Trial Protocol

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

    Alexandra S Zimmer

    *Author for correspondence:

    E-mail Address: alexandra.zimmer@nih.gov

    Women's Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Seth M Steinberg

    Biostatistics & Data Management Section, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Dee Dee Smart

    Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Mark R Gilbert

    Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Terri S Armstrong

    Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Eric Burton

    Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Nicole Houston

    Women's Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Nadia Biassou

    Neuro-Radiology, Clinical Center, NIH, Bethesda, MD 20814, USA

    ,
    Brunilde Gril

    Women's Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    ,
    Priscilla K Brastianos

    Central Nervous System Metastases Program, Massachusetts General Hospital/Harvard Cancer Center Boston, MA 02114, USA

    ,
    Scott Carter

    Biostatistics and Computation Biology, Dana-Farber Cancer Institute, Boston, MA 02114, USA

    ,
    David Lyden

    Pediatric Hematology Oncology, Weill Cornell Medicine, New York, NY 10065, USA

    ,
    Stanley Lipkowitz

    Women's Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    &
    Patricia S Steeg

    Women's Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA

    Published Online:https://doi.org/10.2217/fon-2020-0094

    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).

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