Doxorubicin (Adriamycin) is a commonly used antineoplastic agent whose dosage is limited by a dose-dependent congestive cardiomyopathy. The consequent congestive heart failure may occur during therapy, within a few weeks or even years later. This responds poorly to treatment and is associated with high mortality. Certain risk factors may increase the patient's sensitivity to developing myocardial injury.


Risk factors for doxorubin-associated cardiotoxicity:

(1) age: < 4 years or the elderly

(2) total cumulative dose of doxorubicin

(3) previous radiation therapy to the heart and/or mediastinum

(4) pre-existing heart disease

(5) diabetes mellitus

(6) hypertension

(7) previous therapy with cyclophosphamide (questionable)


Total dose:

(1) If no other risk factors are present, then a patient may receive about 450 mg per square meter with little risk for cardiotoxicity.

(2) If one or more risk factors are present, then congestive heart failure may appear at a lower dose.

(3) The risk for toxicity increases as the total cumulative dose increases: 7% with doses of 550 mg per square meter, 15% with doses of 600 mg per square meter, and 30% with doses of 700 mg per square meter.


NOTE: Batist et al (2001) have demonstrated that liposome-encapsulated doxorubicin is significantly safer than the standard formulation. The appearance of cardiotoxicity occurred at doses > 2,220 mg per square meter with the liposome-encapsulated form vs 480 mg per square meter with the standard formulation. In addition, mucositis and stomatitis was less severe with the liposome formulation.


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