Congestive heart failure in patients treated with doxorubicin: A retrospective analysis of three trials

• Published in: Cancer 2003-06, Vol.97 (11), p.2869-2879
• Main Authors: SWAIN, Sandra M, WHALEY, Fredrick S, EWER, Michael S
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Biological and medical sciences; Doxorubicin - adverse effects; Drug toxicity and drugs side effects treatment; Female; Heart Failure - chemically induced; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Retrospective Studies; Stroke Volume - drug effects; Toxicity: cardiovascular system; Ventricular Function, Left - drug effects
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11407

Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large-scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin-related congestive heart failure (CHF) after a cumulative dose of 550 mg/m(2). To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin-related CHF and the accumulated dose of doxorubicin at which CHF occurs. A group of 630 patients who were randomized to a doxorubicin-plus-placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis. Thirty-two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin-related CHF at a cumulative dose of 550 mg/m(2). Age appeared to be an important risk factor for doxorubicin-related CHF after a cumulative dose of 400 mg/m(2), with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age < or = 65 years). In addition, > 50% of the patients who experienced doxorubicin-related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study. Doxorubicin-related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin.