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

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 > or = 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 < or = 5% at a total A dose < or = 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 < or = 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.