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


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%.


CONCLUSIONS
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.
Gianni
L
L
Unit of Medical Oncology A, Istituto Nazionale Tumori, Milan, Italy. gianni@istitutotumori.mi.it
Dombernowsky
P
P
Sledge
G
G
Martin
M
M
Amadori
D
D
Arbuck
S G
SG
Ravdin
P
P
Brown
M
M
Messina
M
M
Tuck
D
D
Weil
C
C
Winograd
B
B
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D004317:Doxorubicin; D017239:Paclitaxel