ORIGINAL PAPER Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: A single center experience Erkan Dogan • Hikmet Yorgun • Ibrahim Petekkaya • Necla Ozer • Kadri Altundag • Yavuz Ozisik Received: 21 April 2012 / Accepted: 5 May 2012 / Published online: 22 May 2012 Ó Springer Science+Business Media, LLC 2012 Abstract 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 anthra- cycline, 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, electro- cardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase- MB) at baseline and every 9 weeks until disease progres- sion. 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 administra- tion 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. Keywords Breast cancer Á Cardiotoxicity Á Tyrosine kinase inhibitor Á Lapatinib Introduction Cardiotoxicity is one of the well-defined adverse effect of systemic chemotherapy. It was firstly defined by Tan et al. [1] in patients who were treated by doxorubicine in 1967. Many conventional chemotherapeutic drugs may cause cardiotoxicity such as anthracycline, cyclophosphamide, platins, and 5-fluorourasil. In the last decade, a new therapeutic option which is known as targeted therapy has been developed in cancer treatment. Targeted therapy mainly compromises drugs that target tyrosine kinases. These agents fall into two general classes: humanized monoclonal antibodies directed against receptor tyrosine kinases or their ligands and small molecule tyrosine kinase inhibitors (TKIs) [2]. TKIs are small molecules that disrupt the function of kinase activity. They compete with ATP binding site of catalytic domain of E. Dogan Á I. Petekkaya Á K. Altundag (&) Á Y. Ozisik Department of Medical Oncology, Institute of Oncology, Hacettepe University, Sihhiye Ankara 06100, Turkey e-mail: altundag66@yahoo.com H. Yorgun Á N. Ozer Department of Cardiology, Faculty of Medicine, Hacettepe University, Sihhiye Ankara, Turkey 123 Med Oncol (2012) 29:3232–3239 DOI 10.1007/s12032-012-0253-5