HHE Sponsored handbook: Cardioprotection in clinical - Page 3

HHE 2019 3 Anthracyclines Anthracyclines are widely prescribed anticancer agents and remain an important component of treatment guidelines. 1–3 Anthracyclines have been shown to be associated with dose-related cardiotoxicity. 1,3–11 Cardiotoxicity Acute cardiotoxicity occurs in <1% of patients immediately after infusion; early-onset chronic progressive cardiotoxicity presents in 1.6–2.1% of patients, and late-onset chronic progressive cardiotoxicity has been reported in 1.6–5% of patients. 4 This anthracycline-induced cardiotoxicity can impact patients’ treatment and quality of life. 8,12–14 Cardioxane® (dexrazoxane): Prevention of anthracycline-related cardiotoxicity Cardioxane ® is indicated in adults for the prevention of chronic cumulative cardiotoxicity caused by anthracycline use in advanced and/or metastatic breast cancer patients who have received a prior cumulative dose of 300mg/m 2 doxorubicin or a prior cumulative dose of 540mg/m 2 epirubicin when further anthracycline treatment is required. Use in children and adolescents aged 0–18 years is contraindicated unless they are expected to receive a cumulative anthracycline dose equivalent to 300mg/m 2 doxorubicin. The safety and effi cacy of Cardioxane ® in children aged 0–18 years have not been established. > FIGURE 1A Dexrazoxane protects against FAC-induced cardiac events in patients with advanced breast cancer 1 1.0 0.8 0.6 Dexrazoxane 0.4 HR for cardiac event: 3.51 95% Cl: 2.15–5.72 p<0.001 0.2 0.0 Dexrazoxane 102 Placebo 99 300 Placebo 89 92 53 52 500 36 17 29 7 700 17 3 10 1 900 7 1 5 1 1100 3 1 2 1 1300 2 1 1 1500 Study design: All patients received six courses of fl uorouracil, doxorubicin and cyclophosphamide (FAC) plus placebo, total doxorubicin dose 300mg/m 2 . Thereafter they received FAC plus dexrazoxane (n=102) or placebo (n=99). There was no diff erence between groups at baseline in terms of cardiac risk factors. Cardiac events were defi ned as congestive heart failure (CHF) or a decline in left ventricular ejection fraction from baseline ≥20% or from baseline ≥10% and to a value below the lower limit of normal (LLN) or to a value ≥5% below the LLN