Cardiotoxicity trastuzumab

Schneider JW, Chang AY, Garratt A. Trastuzumab cardiotoxicity speculations regarding pathophysiology and targets, for further study. Semin Oncol 2002 29(3 Suppl ll) 22-8. 

Hidalgo S, Albright CA, Wells GL. A case of trastuzumab-assodated cardiomyopathy presenting as an acute coronary syndrome acute trastuzumab cardiotoxicity. Case Rep Cardiol 2013 2013 3. Article ID 473979. http //dx.doi.org/10.1155/2013/473979. 

A higher than expected incidence of CHF is also observed in patients treated with DOX and other cytotoxics (e.g., the taxane paclitaxel) or new generation targeted agents (e.g., the humanized anti-ErbB-2/neu monoclonal antibody trastuzumab) [3]. The cardiotoxic synergism of DOX with taxanes or... 

Trastuzumab-monitorfor cardiotoxicity increases with concur-rent Doxorubicin ... 

Trastuzumab (Herceptin) -humanized mouse monoclonal antibody directed against HER-2/new receptor -fevers, chills, nausea, vomiting, headache during administration -cardiotoxicity (the FDA has not approved concurrent use with doxorubicin)... 

Trastuzumab is well tolerated, but the risk of cardiotoxicity is 5% with single-agent trastuzumab and unacceptably high in combination with an anthracycline. 

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... 

McArthur HL, Chia S. 2007. Cardiotoxicity of trastuzumab in clinical practice. NEJM. 357 94—95. 

Toxicities included an infusion reaction consisting of fever, chills, pain, asthenia, nausea, and vomiting. This syndrome was typically observed after the initial infusion, was self-limited, and frequently did not recur with subsequent infusions. The most serious toxicity was cardiac dysfunction, defined as clinical findings of congestive heart failure and/or subclinical declines in cardiac ejection fraction, which was seen in 5% of patients. Cardiotoxicity was unanticipated, as it had not been detected in previous studies. The mechanism for this effect is unclear, but is likely related to trastuzumab s antiproferative effect on HER2-mediated homeostasis and response to injury. 

This is not to say that cardiotoxicity is not seen with biopharmaceuticals. Cardiomyopathy is now a well-recognized complication of trastuzumab and and has been reported with bevacizumab treatment, in particular in combination with other cytotoxic cancer therapies [20]. Myocarditis and pericarditis are a well-documented complications of vaccinia immunization [21], and could also complicate use of a pox-virus vector for other therapeutics. In 1995 Genetics Institute suspended phase 2 cancer trials of Interleukin-12 for serious tox-icities including cardiac arrhythmia. However, such toxicities are best detected by incorporation of biomarkers for myocardial damage such as troponin-T into preclinical and early clinical studies, and continual ECG monitoring for arrhythmia in preclinical and early clinical studies, not by in vitro explorations of electrophysiology. 

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

DOXORUBICIN TRASTUZUMAB When used in combination, the risk of cardiotoxicity due to trastuzumab is t over fourfold Due to additive cardiotoxic effects Avoid co-administration - except in clinical trials... 

PACLITAXEL TRASTUZUMAB t risk of cardiotoxicity Possibly additive cardiac toxic effect Closely monitor clinically and by ECGs for cardiotoxicity... 

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. 

The mechanism of trastuzumab-induced cardiotoxicity and its synergy with doxorubicin is as yet unknown. However, the cardiac failure responds to standard medical management (122). 

In an attempt to avoid cardiotoxicity after the administration of trastuzumab with doxorubicin, alternative adjuvant regimens have been suggested. Trastuzumab... 

Cardiotoxicity is a major concern with trastuzumab, particularly as it is often used in patients who are receiving or who have previously received anthracychne antibiotics (2). It occurs in 5% of patients given trastuzumab alone, in 13% of patients given trastuzumab with paclitaxel, and in 27% of patients given trastuzumab in combination with anthracyclines and cyclophosphamide (3). 

Suter TM, Cook-Brunsb, Bartonc C. Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer. The Breast. 2004 13(3) 173-183. 

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