Congestive heart failure in patients treated with doxorubicin

We previously reported the results of two Phase III trials of similar design that were initiated in February 1988 and May 1989 that prospectively assessed the cardioprotective efficacy of dexrazoxane in patients who were receiving fluorouracil, doxorubicin, and cyclophosphamide combination therapy for advanced breast carcinoma.2, 3

Sandra M. Swain

2003

Scholarcy highlights

  • 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
  • Thirty‐two of 630 patients had a diagnosis of congestive heart failure
  • We previously reported the results of two Phase III trials of similar design that were initiated in and that prospectively assessed the cardioprotective efficacy of dexrazoxane in patients who were receiving fluorouracil, doxorubicin, and cyclophosphamide combination therapy for advanced breast carcinoma
  • Patients who were included in the current analysis were enrolled in three randomized, double‐blind, multicenter studies that evaluated cardiotoxicity in patients receiving DZR and a doxorubicin‐containing regimen for breast carcinoma or small cell lung carcinoma
  • Patients who received open‐label dexrazoxane were censored at the highest cumulative dose that could have been associated with CHF prior to initiation of open‐label dexrazoxane
  • Circles and crosses indicate censored patients. 95% CI: 95% percent confidence interval
  • We believe that our estimate of doxorubicin‐related CHF is accurate in that it neither underestimates the incidence nor overestimates the incidence by attributing every event of CHF to doxorubicin exposure
  • It is believed that the mechanism for doxorubicin‐related cardiomyopathy is free‐radical formation with subsequent lipid peroxidation. DZR is an antioxidant that functions by chelating iron, thereby reducing iron dependent free‐radical formation. The development of DZR has had the important clinical effect of allowing the delivery of a higher cumulative dose of anthracycline to patients while reducing cardiotoxicity

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