High incidence of cardiovascular mortality caused by acute and early chronic progressive doxorubicin toxicity: Retrospective analysis of 606 patients.

Abstract

e18532 Background: Cardiovascular (CVS) system disorders in Poland are responsible for 52% of all deaths and 18% loss of DALY (disability-adjusted life year), compared to 38% and 11% in US respectively. A retrospective analysis was performed to investigate whether the high incidence of CVS disorders in Poland would translate into increased mortality related to cardiotoxicity of doxorubicin based chemotherapy regimens. Methods: Patients (N=606) from 7 hematological centers received the average of 6.7 (1-11) chemotherapy cycles, with cumulative dose of doxorubicin 330 mg/m2 (range 25 – 850); 146 (24%) patients were subjected to further treatment (transplant or radiotherapy) as consolidation or in relapse. Initial cardiac assessment was based on medical histories including echocardiography in 340 (56%) cases. All patients or they families were additionally questioned at the time of analysis about symptoms and signs of left ventricular failure (LVF), or the causes of death. Results: Acute cardiotoxicity was reported in 32 (5%) patients: ten of them died (1.6%), chemotherapy had to be postponed, prematurely terminated or the doses reduced in further 22 cases (3.4%0. The average Left Vetricular Ejection Fraction (LVEF), assessed by echochardiography decreased from 62% (range 40-85%) at diagnosis to 56% (range 20-75%) at the end of treatment (p<0.001). Cardiac impairment was significantly less pronounced in 30 patients treated with liposomal doxorubicin (average LVEF 56.4 and 54.7 respectively, p< 0.001). At the average observation time of 3 years, early chronic progressive cardiotoxicity was responsible for 18 cardiac deaths (2.9%) and further 81 patients (13.3%) required cardiological treatment including 22(3%) cases of acute coronary syndromes. At the time of analysis 40 (43%) patients died due to disease progression. Conclusions: In our retrospection CVS disorders are already the second most common cause of mortality in lymphoma patients (28/92 – 30% of all deaths, 28/606 – 4.6% of all cases). With the expected increased incidence of late chronic progressive cardiotoxicity we would estimate cardiac mortality to be at least doubled at 10 years.