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Prevention

Persistence, Up to 18 Months of Follow-Up, of Epirubicin-Induced Myocardial Dysfunction Detected Early by Serial Tissue Doppler Echocardiography: Correlation with Inflammatory and Oxidative Stress Markers

^aDepartment of Medical Oncology and ^b Department of Cardiovascular and Neurological Sciences, University of Cagliari, Italy

Key Words. Epirubicin • Myocardial dysfunction • TDI • Inflammatory markers • Oxidative stress markers

Correspondence: Giovanni Mantovani, M.D., Cattedra e Divisione di Oncologia Medica, Università di Cagliari, Azienda Ospedaliero Universitaria di Cagliari, Strada Statale 554, Km 4.500, 09042 Monserrato (Cagliari), Italy: Telephone: 0039-070-5109-6253; Fax: 0039-070-5109-6253; e-mail: mantovan{at}medicina.unica.it

Received July 16, 2008; accepted for publication November 7, 2008; first published online in THE ONCOLOGIST Express on December 5, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

A phase II, open, nonrandomized trial was carried out in a group of epirubicin-treated cancer patients with the aim of detecting early preclinical changes that are predictive of the risk for heart failure. Thirty-one patients (male/female ratio, 8/23; mean age ± standard deviation, 59 ± 14 years) with tumors at different sites and scheduled to be treated with an epirubicin-based chemotherapy regimen, were enrolled. We prospectively evaluated the acute (1 week after) and late (3, 6, 12, and 18 months of follow-up) effects of epirubicin administration. A significant impairment in systolic left ventricular (LV) function was observed at a cumulative epirubicin dose of 200 mg/m². This was shown by a reduction in the strain rate (SR) peak in comparison with baseline and persisted throughout the treatment and follow-up, up to 18 months; strain () remained unchanged. The Sm wave showed a progressive reduction that became significant only at the 18-month follow-up. On TDI the E_m/A_m ratio declined at the 200-mg/m² cumulative epirubicin dose versus baseline and persisted throughout the treatment and up to the 18-month follow-up. On conventional echocardiography the E/A ratio declined significantly only at the 300-mg/m² cumulative epirubicin dose. Interleukin (IL)-6, soluble IL-6 receptor, and reactive oxygen species (ROS) increased significantly at the 200-mg/m² dose, and IL-6 was persistently high at the 300- and 400-mg/m² doses, returning to within baseline values during follow-up. ROS, after the peak reached at the 200-mg/m² dose, returned to within baseline values. A significant inverse correlation between SR and the increase in both IL-6 and ROS was observed. A multiple regression analysis showed that both the IL-6 and ROS variables were independent and strongly predictive of SR. The clinical meaningfulness of our findings warrants further investigations on a larger number of patients for a longer period of follow-up.