替莫唑胺在人表皮生长因子受体 2 阳性乳腺癌脑转移的二级预防中的应用。
Temozolomide in secondary prevention of HER2-positive breast cancer brain metastases.
机构信息
Women's Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20814, USA.
Biostatistics & Data Management Section, National Cancer Institute, NIH, Bethesda, MD 20814, USA.
出版信息
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).
摘要
脑转移发生在多达 25-55%的转移性 HER2 阳性乳腺癌患者中。标准治疗的复发或进展率较高，大多数患者的生存和生活质量受到限制。替莫唑胺（TMZ）已知可穿透血脑屏障，且被美国 FDA 批准用于治疗胶质母细胞瘤。我们的研究小组已经证明，以预防性、节拍式低剂量给予 TMZ 可显著预防乳腺癌小鼠模型中脑转移的发展。基于这些发现，我们开始了一项二级预防临床试验，对 HER2 阳性乳腺癌脑转移患者在近期局部治疗后，给予 TMZ 口服治疗，并联合 T-DM1 进行全身性疾病控制。主要终点是 1 年内无新发脑转移。（NCT03190967）。
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