Clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review

Abstract

This review systematically assessed the evidence on the clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer. We searched eight electronic databases, including Medline and the Cochrane Library, from inception to January 2006 for systematic reviews and randomised controlled trials that reported death, heart failure, arrhythmias or measures of cardiac performance associated with cardioprotective technologies compared with standard treatment in children treated for cancer with anthracyclines. Economic evaluations were also sought. Inclusion criteria, data extraction and quality assessment were undertaken by standard methodology. Four randomised controlled trials met the inclusion criteria of the review; each had methodological limitations. No economic evaluations were identified. Studies were combined through narrative synthesis. One trial found that continuous infusion of doxorubicin did not offer any cardioprotection over rapid infusion. One suggested that continuous infusion of daunorubicin provoked less cardiotoxicity than rapid infusion. One concluded that dexrazoxane reduces cardiac injury during doxorubicin therapy and one reported a protective effect of coenzyme Q 10 on cardiac function during anthracycline therapy. The evidence on the effectiveness of cardioprotective technologies in children is limited in quality and quantity thus making conclusions difficult. This is surprising given the importance of anthracycline use in children with cancer. Further long-term research, which includes relevant outcome measures, is needed to determine whether technologies influence the development of cardiac damage without limiting the antitumour efficacy of anthracyclines.

Activation of Nuclear Factor-κB Pathway by Simvastatin and RhoA Silencing Increases Doxorubicin Cytotoxicity in Human Colon Cancer HT29 Cells

“…As for many other chemotherapeutic agents, the clinical use of doxorubicin is hampered by several side effects, including cardiotoxicity (Bast et al, 2007), which is the major limitation to doxorubicin use and impairs the clinical response and the survival of patients (Bryant et al, 2007). To limit the myocardial damage, less cardiotoxic doxorubicin derivatives (Batist et al, 2001) or the coadministration with cardioprotectors, such as dexrazoxane, coenzyme Q10 (Batist et al, 2001), and flavonoids (Bast et al, 2007), has been proposed without obtaining satisfying results.…”

“…Versus CTRL ϩ doxo: ‫,ء‬ p Ͻ 0.05; ‫,ءء‬ p Ͻ 0.001. Versus SIM:°, p Ͻ 0.05;°°, p Ͻ 0.001. tocols of administration (i.e., continuous infusion versus bolus infusion) have been compared, but none of them significantly reduces adverse effects (Bryant et al, 2007). Rendering cancer cells more sensitive to doxorubicin would be an efficient approach to diminish the overall dose of anthracyclines infused and to increase the ratio between therapeutic effect and toxicity.…”

An initial health economic evaluation of pharmacogenomic testing in patients treated for childhood cancer with anthracyclines

“…It is currently estimated that one in every two cancer patients treated with anthracyclines will develop some degree of cardiac dysfunction, with one in 10 developing CHF that has a mortality rate of about 80% . As these adverse reactions are clinically important and well known, the use of anthracyclines is typically accompanied by a range of preventive and mitigating measures that include dose limitations and schedule modifications, frequent monitoring of cardiac function, and the use of cardioprotective agents . However, specific clinical risk factors such as cumulative anthracycline exposure, age at treatment, sex, and cardiac irradiation provide only limited accuracy in the prediction of anthracycline‐induced cardiotoxicity (ACT) and are therefore inadequate to constitute the basis of optimal therapeutic and follow‐up decisions and for personalizing anthracycline chemotherapy …”

Cardiovascular Complications Caused by Chemotherapy and Targeted Agents

“…Дополнительной проблемой является то, что антра-циклиновая сердечная недостаточность может длительно не проявляться, но развившись, требует пожизненной те-рапии [5,6]. В литературе существует упоминание о раз-витии ЗСН через 20 лет после завершения терапии ААБ.…”