Journal Article10.1002/CNCR.11407
Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials.
TL;DR: 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, which is reflected in the incidence in the broader clinical oncology setting.
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Abstract: BACKGROUND
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/m2. 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.
METHODS
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.
RESULTS
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/m2. Age appeared to be an important risk factor for doxorubicin-related CHF after a cumulative dose of 400 mg/m2, with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age ≤ 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.
CONCLUSIONS
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. Cancer 2003;97:2869–79. © 2003 American Cancer Society.
DOI 10.1002/cncr.11407
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Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response
Charles E. Myers,William McGuire,Robert H. Liss,Ina Ifrim,Karen R. Grotzinger,Robert C. Young +5 more
TL;DR: The results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which consists of binding to DNA, is not antagonized by toCophero and is responsible for tumor response.
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Sewa S. Legha,Robert S. Benjamin,Bruce Mackay,Michael S. Ewer,Sidney Wallace,Manuel Valdivieso,Shelley L. Rasmussen,George R. Blumenschein,Emil J. Freireich +8 more
TL;DR: Cutting peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity, and thus lessen cardiac toxicity, in patients treated by standard intravenous injection.
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Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.
Sandra M. Swain,Fredrick S. Whaley,Miriam C. Gerber,Steven Weisberg,Martin York,Darcy V. Spicer,Stephen E. Jones,Scott Wadler,Ajit Desai,Charles L. Vogel,James L. Speyer,Abraham Mittelman,Sandeep K. Reddy,Kelly Pendergrass,Enrique Velez-Garcia,Michael S. Ewer,Joseph R. Bianchine,Richard A. Gams +17 more
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