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.
