Epirubicin cardiac toxicity

Epirubicin-monitor cumulative dose for cardiac toxicity (not to exceed 1000 mg/M2) vesicant—avoid extravasation... 

Epirubicin is considered to cause substantially less cardiotoxicity than doxorubicin on a molar basis (4,21). This has been attributed to its more rapid clearance rather than a different action (22). In a randomized, double-blind comparison of epirubicin and doxorubicin, there was a significant reduction in left ventricle ejection fraction with doxorubicin but not with epirubicin (23). However, data from large clinical series and from morphological examination of endomyocardial biopsies in smaller series of patients suggest that the incidence and severity of cumulative cardiac toxicity associated with epirubicin 900 mg/m is similar to that associated with doxorubicin 450-550 mg/raf (24). In 29 patients treated with epirubicin in cumulative doses ranging... 

The major toxicities of these four groups are bone marrow depression, nausea and vomiting, mucositis, and diarrhea. Daunorubicin, doxorubicin, epirubicin, idarubicin, and to a lesser extent, mitoxantrone, cause cardiac toxicity. Mitomycin and bleomycin cause... 

Cardiomyopathy is the most common chemotherapy-associated cardiac toxicity. Myocardial ischemia, pericarditis, arrhythmias, miscellaneous electrocardiogram (ECG) changes, and angina occur much less frequently. The anthracyclines (da-unorubicin, doxorubicin, epirubicin, and idarubicin) have the highest consistent risk for cardiomyopathy, which is cumulative dose related. There is evidence that high-dose cyclophosphamide, mitoxantrone, and fluorouracil also pose an increased risk of cardiac damage. The concurrent use of traztuzu-mab with an anthracycline and cyclophosphamide is associated with a risk of cardiac dysfunction, but the consequences of sequential use are not yet known. 

Studies in mice have found that the taxanes docetaxel and paclitaxel, and the vehicle used for paclitaxel Cremophor, may all modify the distribution and metabolism of doxorubicin increasing its levels in the heart, liver and kidneys. This may contribute to the cardiac toxicity seen during use with paclitaxel. Similarly, m vitro studies in human myocardium showed that paclitaxel and docetaxel increased the conversion of doxorubicin to doxorubicinol, the metabolite that is thought to be responsible for cardiotoxicity. An in vitro study on the effect of paclitaxel and Cremophor on epirubicin metabolism in human blood found that paclitaxel slightly decreased production of epirubicinol. A marked inhibition of epirubicinol production occurred in the presence of Cremophor, hut because of the low... 

It is worth noting that PEG-poly (aspartate) block copolymers containing a epirubicin-hydrazone conjugate also showed higher tumor accumulation over free drug and decreased cardiac toxicity are in a Phase I clinical trial, suggesting the potential of prodrug incorporation in micelles for cancer therapy [60]. 

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