Ther Clin Risk Manag. 2007 Aug;3(4):665-73.
Breast cancer remains a leading cause of disease and death among women throughout the world. Despite advances in drug therapy, development of novel and improved drugs for breast cancer continues to be of great interest. Lapatinib is a novel dual receptor tyrosine kinase inhibitor that is a selective and potent inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, both of which are growth promoting factors overexpressed in some breast cancers. Cell-based assays have proven lapatinib to be a potent inhibitor of ErbB-1 and ErbB-2 activation and breast cancer cell proliferation. In pharmacokinetic studies, lapatinib has shown mostly linear elimination kinetics over the daily dose range of 10-1600 mg and is metabolized by CYP3A4/5 and CYP2C19. Phase I, II, and III clinical trials involving lapatinib as monotherapy or in combination have shown promise for the treatment of advanced and metastatic breast cancer. Drug-drug interactions may occur secondary to concomitant administration of either CYP450 inhibitors or inducers. While lapatinib appear to be a promising addition to breast cancer therapy, several questions remain to be answered before its optimal role is elucidated.
乳腺癌仍然是全世界女性疾病和死亡的主要原因。尽管药物治疗取得了进展，但开发新型和改进的乳腺癌药物仍然是人们非常关注的问题。拉帕替尼是一种新型的双重受体酪氨酸激酶抑制剂，对 ErbB-1 和 ErbB-2 酪氨酸激酶具有选择性和强大的抑制作用，这两种激酶都是在一些乳腺癌中过度表达的促进生长的因素。基于细胞的测定已证明拉帕替尼是 ErbB-1 和 ErbB-2 激活和乳腺癌细胞增殖的有效抑制剂。在药代动力学研究中，拉帕替尼在 10-1600mg 每日剂量范围内表现出主要线性消除动力学，并且由 CYP3A4/5 和 CYP2C19 代谢。涉及拉帕替尼单药或联合治疗的 I、II 和 III 期临床试验显示出治疗晚期和转移性乳腺癌的前景。由于同时给予 CYP450 抑制剂或诱导剂，可能会发生药物相互作用。虽然拉帕替尼似乎是乳腺癌治疗的一个有前途的补充，但在阐明其最佳作用之前，仍有几个问题需要回答。
