Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer
Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer
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DOI：
10.1093/jnci/djh131
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发表时间：
2004-05-19
影响因子：
10.3
通讯作者：
Slamon, DJ
中科院分区：
文献类型：
--
作者：
Pegram, MD;Konecny, GE;Slamon, DJ
背景资料。曲妥珠单抗是一种人源化的抗HER2抗体，它增加了过度表达HER2的转移性乳腺癌患者一线化疗的临床益处。我们描述了曲妥珠单抗与乳腺癌治疗中常用化疗药物之间的相互作用。方法：采用多药效应/联合指数等值线分析方法，研究化疗药物联合曲妥珠单抗对4种HER2高表达乳腺癌细胞株SK-BR-3、BT-474、MDA-MB-361和MDA-MB-453的抑制作用。组合指数值由中位效应图的参数得出，并使用统计检验来确定多个效应水平的平均组合指数值是否与组合指数值1.0在统计学上有显著差异。小于1.0的值表示协同交互，大于1.0的值表示拮抗交互，等于1.0的值。表示相加交互作用。结果：在较大的临床可达药物浓度范围内，曲妥珠单抗联合卡铂对四种乳腺癌细胞株均有协同作用(平均联合指数为0.32[P
Background. Trastuzumab, a humanized anti-HER2 antibody, increases the clinical benefit of first-line chemotherapy in patients with metastatic breast cancers that overexpress HER2. We characterized interactions between trastuzumab and chemotherapeutic agents commonly used in the treatment of breast cancer. Methods: Multiple drug effect/combination index isobologram analysis was used to study the efficacy of chemotherapeutic drug plus trastuzumab combinations tested against four HER2-overexpressing breast cancer cell lines (SK-BR-3, BT-474, MDA-MB-361, and MDA-MB-453). Combination index values were derived from parameters of the median effect plots, and statistical tests were used to determine whether the mean combination index values at multiple effect levels were statistically significantly different from a combination index value of 1.0. Values less than 1.0 indicate synergistic interactions, values greater than 1.0 indicate antagonistic interactions, and values equal to 1.0. indicate additive interactions. Results: At a wide range of clinically achievable drug concentrations, synergistic interactions were observed in all four breast cancer cell lines for trastuzumab plus carboplatin (mean combination index values ranged from 0.32 [P