L. Gianni et al., Cardiac function following combination therapy with paclitaxel and doxorubicin: An analysis of 657 women with advanced breast cancer, ANN ONCOL, 12(8), 2001, pp. 1067-1073
Background: To determine the cardiotoxicity of paclitaxel (T) plus doxorubi
cin (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 vent
ricular ejection fraction [LVEF] decrease greater than or equal to 20% or t
o < 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 p
atients at a median of 17.3 months after diagnosis (range 4.1-31.2 months).
The risk of developing CHF was less than or equal to5% at a total A dose l
ess than or equal to 380 mg/m(2). In patients who received a total A dose >
440 mg/m(2), the incidence of CHF was > 25% but similar to that of A monot
herapy. The risk of CHF was similar in women receiving AT or A monotherapy
at a dose less than or equal to 380 mg/m(2) (2%-3%). LVEF progressively dec
reased in patients who received AT, especially at a cumulative A dose > 380
mg/m(2). 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 wo
men who developed LVEF < 50%.
Conclusion: The reported cardiac effects are consistent with anthracycline-
related cardiotoxicity. AT is associated with a cardiac risk similar to tha
t of A monotherapy up to a cumulative A dose of 340-380 mg/m(2).