Doxorubicin causes congestive heart failure more often and at lower cumulative doses than previously thought, according to a review to appear in the June 1st print issue of CANCER and that has been available since May 19th online.

In addition, the authors noted that baseline measurement of left ventricular ejection fraction may not be as accurate a predictor of doxorubicin-induced heart failure as previously thought. Their data indicate that risk for congestive heart failure after a cumulative dose of 400 mg/m2 is higher for patients over 65 years of age.

The authors urge clinicians to reconsider how they monitor and treat cancer patients: “Patients of advanced age may be at higher risk for congestive heart failure and may benefit from administration of a cardioprotective or the use of doxorubicin as an infusion.”

The most recent published work on doxorubicin-induced heart failure estimated the incidence of the condition to be 2.2 percent. However, the authors noted that limitations in study design could lead to an underestimation of incidence rate.

In the current study, Swain and her colleagues analyzed data from 3 previous studies that included 630 patients in order to examine relationships between cumulative doxorubicin dose and risk for developing congestive heart failure and to examine any drug effects on left ventricular ejection fraction during chemotherapy treatment.

Of the 630 total patients, 32 (5.1 percent) developed congestive heart failure, more than 2 times the 2.2 percent incidence rate reported previously. Most cases developed at cumulative doses of 500 mg/m2, but some were observed at doses as low as 300 mg/m2. Overall, the estimated cumulative percentage of patients with congestive heart failure was 5 percent at a cumulative dose of 400 mg/m2, rising to 16 percent at 500 mg/m2, 26 percent at 550 mg/m2, and 48 percent at 700 mg/m2.

Degree of heart failure was roughly evenly distributed between mild (38 percent), moderate (34 percent), and severe (28 percent). The majority of patients (66 percent) experienced less than 30 percent decline from baseline ejection fraction --- a decrease considered by many to be the cutoff point for risk of heart failure.

The authors identified age over 65 years as a risk factor for drug-induced failure. When compared with younger patients, these older patients had 3.28 times the risk for development of failure at a cumulative dose higher than 400 mg/m2.

The researchers concluded, “Analysis of prospective data from phase III trials indicates that doxorubicin-induced congestive heart failure occurs with greater frequency than was previously reported.” They added, “It is critical both to identify an accurate means of predicting this serious side effect and to explore ways to further reduce cardiotoxicity.”