Braman Family Breast Cancer institute, University of Miami Sylvester Comprehensive Cancer Center, USA.
Braman Family Breast Cancer institute, University of Miami Sylvester Comprehensive Cancer Center, USA ; Division of Hematology/Oncology, University of Miami Sylvester Comprehensive Cancer Center, USA ; Departments of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Breast Cancer (Dove Med Press). 2010 Nov 15;2:79-91. doi: 10.2147/BCTT.S5929.
Approximately 20% of new diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (EGFR2), also known as erythroblastic leukemia viral oncogene homolog 2 (ERBB2) protein, as a consequence of ERBB2 gene amplification, resulting in a poor prognosis. Clinical outcome can be substantially improved by ERBB2-targeted therapy. Lapatinib is a potent, orally bioavailable small molecule that reversibly and selectively inhibits epidermal growth factor receptor (EGFR1 or ERBB1) and ERBB2 tyrosine kinases. Lapatinib binds the adenosine triphosphate-binding site of the receptor's intracellular domain to inhibit tumor cell growth. This review summarizes the pharmacology, pharmacokinetics, efficacy, and tolerability of lapatinib, and reviews both Food and Drug Administration-approved and investigational uses of lapatinib in breast cancer therapy. The drug is generally well tolerated in patients, with diarrhea and rashes being the most common (usually mild or moderate) adverse effects. Unlike trastuzumab, lapatinib has infrequent adverse effects on cardiac function. Lapatinib has substantial activity for advanced ERBB2-positive breast cancer, particularly in combination with capecitabine, following progression after anthracyclines, taxanes, and trastuzumab. Lapatinib combined with capecitabine yielded significant improvements in time to progression and response rate compared with capecitabine alone. This drug can also be combined with letrozole for the treatment of postmenopausal women with ERBB2-positive breast cancer, for whom hormonal therapy is indicated. Lapatinib has shown early promise in treatment of central nervous system metastasis and is being further evaluated in various clinical settings.
约 20%的新诊断乳腺癌过表达人表皮生长因子受体 2（EGFR2），也称为红细胞白血病病毒致癌基因同系物 2（ERBB2）蛋白，这是由于 ERBB2 基因扩增导致的，预后较差。通过 ERBB2 靶向治疗可以显著改善临床结局。拉帕替尼是一种有效的、口服生物利用的小分子，可可逆且选择性地抑制表皮生长因子受体（EGFR1 或 ERBB1）和 ERBB2 酪氨酸激酶。拉帕替尼结合受体细胞内结构域的三磷酸腺苷结合位点，抑制肿瘤细胞生长。本文总结了拉帕替尼的药理学、药代动力学、疗效和耐受性，并回顾了拉帕替尼在乳腺癌治疗中 FDA 批准和研究性应用。该药在患者中通常具有良好的耐受性，最常见（通常为轻度或中度）的不良反应是腹泻和皮疹。与曲妥珠单抗不同，拉帕替尼对心脏功能的不良影响较少。拉帕替尼对晚期 ERBB2 阳性乳腺癌具有显著活性，特别是在蒽环类药物、紫杉烷类药物和曲妥珠单抗治疗进展后与卡培他滨联合使用时。与卡培他滨单药治疗相比，拉帕替尼联合卡培他滨可显著改善进展时间和缓解率。该药还可与来曲唑联合用于治疗 ERBB2 阳性乳腺癌的绝经后妇女，这些患者需要激素治疗。拉帕替尼在治疗中枢神经系统转移方面显示出早期的前景，并正在各种临床环境中进一步评估。
