Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients.
Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients.
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DOI：
10.1038/sj.bjc.6605918
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发表时间：
2010-10-26
影响因子：
8.8
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中科院分区：
文献类型：
--
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曲妥珠单抗诱导人表皮生长因子受体 2 阳性 (HER2+) 肿瘤消退的拟议机制之一包括促进抗体依赖性细胞介导的细胞毒性 (ADCC)。粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 介导 ADCC。我们介绍了在曲妥珠单抗中添加 GM-CSF 治疗曲妥珠单抗耐药 HER2+ 转移性乳腺癌患者的初步研究。曲妥珠单抗+/-化疗后进展的 HER2+ 转移性乳腺癌患者继续每周静脉注射曲妥珠单抗 2mg kg–1，每天皮下注射 GM-CSF 250μgm–2。每 8 周评估一次患者的反应。继续治疗直至疾病进展或出现无法耐受的毒性。 17 名患者可进行评估（中位年龄 48 岁，范围 27-75 岁）。转移部位的中位数为 2 个（范围 1-3）；最常见的部位是肝脏（n=10）。转移性疾病既往治疗方案的中位数为 2（范围 1-5）。未观察到客观疾病反应，但 5 名患者 (29%) 疾病稳定，中位持续时间为 15.8（范围 10-53.9）周。最常见的不良事件是注射部位出现皮疹。未发现 4 级或不可逆不良事件。对于曲妥珠单抗耐药的 HER2+ 转移性乳腺癌患者，单独在曲妥珠单抗中添加 GM-CSF 具有适度的临床益处和可接受的安全性。
One of the proposed mechanisms of trastuzumab-induced regression of human epidermal growth factor receptor 2-positive (HER2+) tumours includes facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates ADCC. We presented our pilot study of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer. Patients with HER2+ metastatic breast cancer that progressed after trastuzumab +/− chemotherapy were continued on trastuzumab 2 mg kg–1 intravenous weekly and GM-CSF 250 μg m–2 subcutaneous daily. Patients were assessed for response every 8 weeks. Treatment was continued until disease progression or intolerable toxicity. Seventeen patients were evaluable (median age 48 years, range 27–75 years). The median number of metastatic sites was 2 (range 1–3); the most common site was the liver (n=10). The median number of prior regimens for metastatic disease was 2 (range 1–5). No objective disease response was observed, but five patients (29%) had stable disease for a median duration of 15.8 (range 10–53.9) weeks. The most common adverse event was rash at the injection site. No grade 4 or irreversible adverse event was seen. The addition of GM-CSF to trastuzumab alone had a modest clinical benefit and acceptable safety profile in heavily pretreated patients with trastuzumab-resistant HER2+ metastatic breast cancer.
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