Cardiac function following combination therapy with paclitaxel and doxorubicin: An analysis of 657 women with advanced breast cancer

L. Gianni, P. Dombernowsky, G. Sledge, M. Martin, D. Amadori, S. G. Arbuck, P. Ravdin, M. Brown, M. Messina, D. Tuck, C. Weil, B. Winograd

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Abstract

Background: To determine the cardiotoxicity of paclitaxel (T) plus doxorubicin (A) combination therapy in women with advanced breast cancer. To define a dose range of A for use in AT. Patients and methods: The effect of cumulative A dose on risk of congestive heart failure (CHF) and alterations of myocardial contractility (left ventricular ejection fraction [LVEF] decrease ≥ 20% or to <50%) was estimated from pooled data from 10 trials of AT. Results: Thirty-one of 657 patients (4.7%) developed CHF at a median of 6.6 months (range 0.3-24.6) after initiation of AT. CHF was stabilized in 29 patients at a median of 17.3 months after diagnosis (range 4.1-31.2 months). The risk of developing CHF was ≤ 5% at a total A dose ≤ 380 mg/m2. In patients who received a total A dose > 440 mg/m2, the incidence of CHF was > 25% but similar to that of A monotherapy. The risk of CHF was similar in women receiving AT or A monotherapy at a dose ≤ 380 mg/m2 (2%-3%). LVEF progressively decreased in patients who received AT, especially at a cumulative A dose > 380 mg/m2. LVEF decreases were more frequent in patients who later developed CHF, but the majority of CHF patients did not experience LVEF alterations prior to symptoms. LVEF recovered after discontinuation of A in 25 of 67 women who developed LVEF <50%. Conclusion: The reported cardiac effects are consistent with anthracycline-related cardiotoxicity. AT is associated with a cardiac risk similar to that of A monotherapy up to a cumulative A dose of 340-380 mg/m2.

Original languageEnglish
Pages (from-to)1067-1073
Number of pages7
JournalAnnals of Oncology
Volume12
Issue number8
DOIs
Publication statusPublished - 2001

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Keywords

  • Breast cancer
  • Cardiac toxicity
  • Doxorubicin
  • Paclitaxel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gianni, L., Dombernowsky, P., Sledge, G., Martin, M., Amadori, D., Arbuck, S. G., Ravdin, P., Brown, M., Messina, M., Tuck, D., Weil, C., & Winograd, B. (2001). Cardiac function following combination therapy with paclitaxel and doxorubicin: An analysis of 657 women with advanced breast cancer. Annals of Oncology, 12(8), 1067-1073. https://doi.org/10.1023/A:1011655503511