Abstract 1209: Concurrent administration of doxorubicin and lapatinib worsens doxorubicin-induced cardiac dysfunction in mice

Background: Concurrent use of chemotherapy drug doxorubicin (DOX) and Trastuzumab, a monocloncal antibody that blocks HER2, induced cardiac dysfunction in 27% of patients. Clinical trials have shown that the incidence of symptomatic heart failure was much lower (0.3%) in patients sequentially treated with DOX and lapatinib, an EGFR and HER2 tyrosine kinase inhibitor. More studies are necessary to determine the safety of concurrent DOX and lapatinib treatment, which is important for developing more effective cancer therapy. Here, we tested the effect of concurrent DOX and lapatinib administration on cardiac function in mice. Methods: A well-established subacute murine DOX heart failure model was used. 10-12 week old C57BL/6 mice were treated with a single dose of DOX (20 mg/kg, i.p.), or DOX concurrently with lapatinib (100 mg/kg, oral gavage, daily). Survival was analyzed by the Kaplan-Meier method. Cardiac function was monitored by hemodynamic measurements. Results: Ten days after the treatment, survival was significantly lower in DOX+lapatinib vs. DOX mice (13 vs. 0 %, n=7-8 /group, P