Bilancia D, Rosati G, Dinota A, Germano D, Romano R, Manzione L
Medical Oncology Unit, San Carlo Hospital, Potenza, Italy.
Ann Oncol. 2007 Jun;18 Suppl 6:vi26-30. doi: 10.1093/annonc/mdm220.
Aberrant activation of some members of human epidermal growth factor receptor (HER) family plays a key role in breast carcinogenesis. Lapatinib is an oral dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor (EGFR/ErbB1) and HER2/ErbB2. Having more targets, probably its antitumor activity could be more efficient. Clinical data have shown that lapatinib is active in HER2-positive breast cancer as monotherapy, in combination with trastuzumab, and in trastuzumab-resistant patients. Phase I clinical trials have shown also that lapatinib is well tolerated, with mild diarrhea and skin rush as common toxic effects and low incidence of cardiotoxicity. Phase II and III clinical trials' data provide encouraging evidence of the clinical effectiveness of lapatinib in advanced or metastatic breast cancer and for its potential in patients with brain metastases. Interim results from the large, phase III trial in 392 patients showed that in combination with capecitabine lapatinib almost doubled time to progression when compared with capecitabine alone. Several clinical trials that explore the efficacy of lapatinib in combination with conventional chemotherapeutic agents [paclitaxel (Taxol), capecitabine and platinoids], hormonotherapy and other target therapies are ongoing in advanced breast cancer or in neo-adjuvant and adjuvant settings. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes are allowing us to bring patient-specific novel therapies such as lapatinib to the clinic.
人表皮生长因子受体（HER）家族某些成员的异常激活在乳腺癌发生过程中起关键作用。拉帕替尼是一种口服双靶点酪氨酸激酶抑制剂，可选择性抑制表皮生长因子受体（EGFR/ErbB1）和HER2/ErbB2。由于具有更多靶点，其抗肿瘤活性可能更高。临床数据表明，拉帕替尼作为单一疗法、与曲妥珠单抗联合使用以及用于曲妥珠单抗耐药患者时，在HER2阳性乳腺癌中均具有活性。I期临床试验还表明，拉帕替尼耐受性良好，常见的毒性作用为轻度腹泻和皮疹，心脏毒性发生率较低。II期和III期临床试验数据为拉帕替尼在晚期或转移性乳腺癌中的临床有效性及其在脑转移患者中的潜力提供了令人鼓舞的证据。一项针对392例患者的大型III期试验的中期结果显示，与单独使用卡培他滨相比，拉帕替尼联合卡培他滨可使疾病进展时间几乎翻倍。目前，在晚期乳腺癌或新辅助及辅助治疗中，有几项临床试验正在探索拉帕替尼与传统化疗药物[紫杉醇（泰素）、卡培他滨和铂类药物]、激素疗法及其他靶向疗法联合使用的疗效。我们对乳腺癌生物学特性的深入了解以及利用生物标志物识别特定亚型，使我们能够将拉帕替尼等针对患者个体的新型疗法应用于临床。
