Yardley Denise A, Raefsky Eric, Hainsworth John D, Burris Howard A, Priego Victor, Inclan Alejandro
Sarah Cannon Research Institute, 250 25th Avenue North, Suite 100, Nashville, TN, USA,
Breast Cancer Res Treat. 2014 Dec;148(3):535-40. doi: 10.1007/s10549-014-3189-y. Epub 2014 Nov 6.
Amrubicin is a synthetic anthracycline which has been shown in preclinical studies to have broad-spectrum anti-tumor activity and a lower potential for cardiotoxicity as compared to doxorubicin. We conducted a phase 1/2 trial of single-agent amrubicin as second- or third-line treatment for women with metastatic breast cancer. Women with metastatic HER2-negative breast cancer who had normal cardiac function and measurable disease, received intravenous (IV) amrubicin every 3 weeks. Prophylactic treatment with granulocyte colony-stimulating factors (G-CSFs) was recommended. Escalating amrubicin doses were administered in a 3 + 3 design in the phase 1 portion to determine the maximum tolerated dose. Achievement of a median PFS ≥4.5 months would warrant further development of amrubicin in this setting. Seventy-eight women (median age 58 years) were treated (phase 1, 15 patients; phase 2, 63 patients). An amrubicin dose of 110 mg/m(2) every 3 weeks was selected as the phase 2 dose, and 66 patients were treated. Twelve of 66 patients (18%) achieved objective response, and the clinical benefit rate was 42%. Median PFS was 4 months (95% CI 2.5, 5.8). Neutropenia was the most common grade 3/4 toxicity, observed in 29 patients (44%). One patient experienced an asymptomatic transient left ventricular ejection fraction decline (grade 3). Although the study did not meet the predefined PFS, amrubicin was well tolerated at 110 mg/m(2) IV when administered every 3 weeks with prophylactic G-CSF, and was an active second- or third-line treatment for metastatic HER2-negative breast cancer.
氨柔比星是一种合成蒽环类药物，临床前研究表明其具有广谱抗肿瘤活性，与多柔比星相比，心脏毒性较低。我们开展了一项1/2期试验，评估单药氨柔比星作为转移性乳腺癌女性患者二线或三线治疗的疗效。转移性HER2阴性乳腺癌且心功能正常、疾病可测量的女性患者，每3周接受一次静脉注射氨柔比星治疗。推荐使用粒细胞集落刺激因子（G-CSF）进行预防性治疗。在1期试验部分，采用3+3设计递增氨柔比星剂量，以确定最大耐受剂量。若中位无进展生存期（PFS）≥4.5个月，则支持氨柔比星在此情况下进一步开展研究。78名女性患者（中位年龄58岁）接受了治疗（1期15例，2期63例）。选择每3周110mg/m²的氨柔比星剂量作为2期试验剂量，66例患者接受了治疗。66例患者中有12例（18%）获得客观缓解，临床获益率为42%。中位PFS为4个月（95%CI 2.5，5.8）。中性粒细胞减少是最常见的3/4级毒性反应，29例患者（44%）出现该反应。1例患者出现无症状性短暂左心室射血分数下降（3级）。尽管该研究未达到预设的PFS，但每3周静脉注射110mg/m²氨柔比星并联合预防性G-CSF时耐受性良好，是转移性HER2阴性乳腺癌的一种有效的二线或三线治疗方案。
