Department of Medical Oncology, Institute of Oncology, Hacettepe University, Sihhiye Ankara, 06100, Turkey.
Med Oncol. 2012 Dec;29(5):3232-9. doi: 10.1007/s12032-012-0253-5. Epub 2012 May 22.
Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg/m(2) in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3-60) weeks. The median age was 48 (range 28-83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had T wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK-MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK-MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.
拉帕替尼是一种双重酪氨酸激酶抑制剂（TKI），对 ErbB2 阳性转移性乳腺癌（MBC）具有显著疗效。先前的研究表明，TKI 会导致约 10%的患者出现心脏毒性。本研究评估了拉帕替尼在 ErbB2 阳性 MBC 女性中的心脏安全性。在这项观察性单中心研究中，所有先前在辅助和/或转移性环境中接受过蒽环类药物、紫杉烷类药物和曲妥珠单抗治疗的 ErbB2 阳性 MBC 患者被分配接受拉帕替尼治疗，剂量为 1250mg 每日 1 次，同时卡培他滨剂量为 2000mg/m2，分 2 次服用，第 1 天至第 14 天，每 21 天为 1 个周期。在疾病进展之前，通过症状、胸超声心动图、心电图和生化标志物（脑利钠肽（BNP）、肌酸激酶（CK）和肌酸激酶同工酶（CK-MB））在基线和每 9 周评估心脏毒性。26 例患者接受拉帕替尼联合卡培他滨治疗，中位时间为 18（范围 3-60）周。中位年龄为 48（范围 28-83）岁。所有患者均患有 ErbB2 阳性 MBC。在 25 例符合条件的患者中，与基线相比，有 5（19.2%）例患者出现新的心脏事件。这 5 例患者中，1 例（3.8%）出现 T 波倒置，1 例（3.8%）出现窦性心动过速，1 例（3.8%）出现 QT 间期延长（453ms），2 例（7.7%）出现 LVEF 低于临界值。在 21 例符合条件的患者中，与基线相比，有 2（7.7%）例患者 BNP 升高，1（3.8%）例患者 CK 升高，1（3.8%）例患者 CK-MB 升高。没有发生需要监测或治疗的严重心脏事件。拉帕替尼给药时间与 LVEF 变化、QT 间期延长、BNP、CK 和 CK-MB 水平之间无统计学显著关系。根据我们的研究结果，拉帕替尼安全且耐受性良好，心脏副作用发生率低。因此，曲妥珠单抗似乎不是 TKI 的类效应。然而，尽管在拉帕替尼治疗下没有临床显著的心脏不良影响，但本研究报告的心脏毒性发生率高于先前的拉帕替尼研究。
