Cardiotoxicity docetaxel

Trastuzumab is licensed for the treatment of early breast cancer that overexpresses human epidermal growth factor receptor-2 (HER2). It may be administered as monotherapy or in combination with, for example, paclitaxel, docetaxel (taxanes) or anastrozole (aromatase inhibitors). Since trastuzumab can cause cardiotoxicity, concomitant use with anthracyclines such as... 

Cardiotoxicity Heart failure has been observed in patients receiving trastuzumab therapy alone or in combination with paclitaxel or docetaxel,... 

An interaction of doxorubicin with the anti-HER2 receptor humanized monoclonal antibody, trastuzumab (Herceptin), has been reported. Most patients who received trastuzumab in early trials had been pretreated with anthracyclines. Despite this, preliminary information suggested that reduced systolic cardiac function was an adverse effect of trastuzumab (119). More recently, this problem has been further highlighted in a study of women with metastatic breast cancer (120). Patients who had not received prior anthracycline-containing adjuvant chemotherapy were at greater risk of cardiotoxicity when they received trastuzumab in combination with doxorubicin or cyclophosphamide (27 and 75% respectively), compared with only 11% of patients who received trastuzumab in combination with pachtaxel (120,121). The risk of cardiac events in patients treated with doxorubicin, cyclophosphamide, and trastuzumab increased markedly after a cumulative doxorubicin dose of 360 mg/m. This suggests synergistic cardiotoxicity with trastuzumab and doxorubicin. Trastuzumab is therefore currently licensed only for use in conjunction with pacli-taxel or docetaxel and not with conventional doxorubicin. 

In an attempt to clarify further the cardiotoxicity of paclitaxel, its effect on cardiovascular autonomic regulation has been investigated in 14 women (21). The authors concluded that autonomic modulation of heart rate is impaired by paclitaxel, but they were unable to say whether it would return to normal on withdrawal. They also investigated the effect of docetaxel on neural... 

Schedules for optimal use alone or in combination with other drugs, including doxorubicin and cisplatin, still are evolving. Drug interactions have been noted the sequence of cisplatin preceding paclitaxel decreases paclitaxel clearance and produces greater toxicity than the opposite schedule. Paclitaxel decreases doxorubicin clearance and enhances cardiotoxicity, whereas docetaxel has no apparent effect on anthracycline pharmacokinetics. 

Toxicity associated with combinations of paclitaxel with doxorubicin or epirubicin depends on the order of administration. Some modest pharmacokinetic changes may occur when paclitaxel and epirubicin are given together. The combination of doxorubicin and pacUtaxel is more cardiotoxic than doxorubicin alone paclitaxel increases doxorubicin levels but doxorubicin does not alter pacUtaxel levels. Docetaxel may modestly affect the pharmacokinetics of epirubicin and doxorubicin. 

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... 

Taxanes Paclitaxel (853 Da) Docetaxel (861 Da) Sinus bradycardia, ventricular arrhythmias, myocardial ischemia, LV dysfunction, enhanced anthracycline cardiotoxicity... 

Cardiovascular Heart failure (New York Heart Association classes II-IV) has been observed in patients receiving trastuzumab, alone or in combination with paclitaxel or docetaxel, particularly after chemotherapy containing an anthracycline (doxorubicin or epirubicin) [303, 304, 305, 306. It can be moderate or severe and can be fatal. The results of many randomized trials have shown that the degree of cardiotoxicity is generally acceptable the incidence of cardiac damage caused by trastuzumab was 0.4-4.1% [307 ]. Older age, lower left ventricular ejection fraction, and antihypertensive medications are associated with an increased risk of cardiac dysfunction in patients receiving trastuzumab [308 "]. The cardiac dysfunction associated with trastuzumab is usually reversible on withdrawal and standard medical therapy [309 ]. In one case, trastuzumab-associated cardiomyopathy presented with complete left bundle-branch block mimicking acute coronary syndrome [310" ]. 

Cardiovascular There are no significant reports of cardiotoxicity associated with docetaxel. The combination of docetaxel + trastuzumab is not associated with significant cardiotoxicity [122 ]. Patients who are... 

Unlike paclitaxel, docetaxel does not appear to affect the metabolism of doxorubicin. Thus, the combination of docetaxel arul doxorubicin does not increase the risk of cardiotoxicity, compared with doxorubicin alone [145 ] or doxorubicin + cyclophosphamide combination chemotherapy [146 ]. 

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