Pretreatment with Tamoxifen does not Change Acute Epirubicin Cardiotoxicity in Rats

Abstract

The use of anthracycline antibiotics as anticancer agents is limited by a cumulative dose-related cardiotoxicity (Wojtacki et al. 2000). Tamoxifen, a synthetic non-steroidal antioestrogen, in addition to its application in treatment and prevention of breast cancer, is also a modulator of multidrug resistance and an antioxidant (Perumal et al. 2005). Combination of epirubicin and tamoxifen has been used in breast cancer (Pico et al. 2004) and lung cancer therapy (Chen et al. 2000). Furthermore, high-dose tamoxifen have been used in phase I trials in patients with advanced malignancies (Perez et al. 2003). Clinical studies have not reported any increased cardiotoxicity with the combination that outweighs beneficial effects (Wils et al. 1999; Fargeot et al. 2004; Pico et al. 2004). Due to its multiple properties, tamoxifen can reverse resistance to anthracyclines (Lucci et al. 1999), but the possibility of increased cardiotoxicity of anthracyclines may represent a clinical problem. In this preliminary study the combination was examined in an isolated rat heart model.