Congestive heart failure in patients treated with doxorubicin

TLDR

Doxorubicin is a potent cytotoxic agent whose use is limited by dose‑dependent cardiotoxicity, with a retrospective study reporting a 7 % incidence of congestive heart failure after 550 mg/m². The study aimed to determine whether the 7 % CHF incidence at 550 mg/m² applies to a broader oncology population by evaluating data from three prospective Phase III trials. The authors analyzed 630 patients randomized to doxorubicin plus placebo across two breast cancer and one small‑cell lung cancer trials, identifying 32 cases of CHF. The analysis found that 26 % of patients developed doxorubicin‑related CHF at 550 mg/m², with older patients (>65 yr) at higher risk after 400 mg/m², over half of CHF cases showing <30 % LVEF decline, indicating that CHF occurs more frequently and at lower doses than previously reported and that LVEF is an unreliable predictor.

Abstract

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.