Doxorubicin-paclitaxel: a safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial.
BACKGROUND
The potential cardiotoxicity of the doxorubicin-paclitaxel regimen, when paclitaxel is given shortly after the end of the anthracycline infusion, is an issue of concern, as suggested by small single institution Phase II studies.


METHODS
In a large multicenter Phase III trial, 275 anthracycline naive metastatic breast carcinoma patients were randomized to receive either doxorubicin (60 mg/m(2)) followed 30 minutes later by paclitaxel (175 mg/m(2) 3-hour infusion; AT) or a standard doxorubicin-cyclophosphamide regimen (AC; 60/600 mg/m(2)). Both treatments were given once every 3 weeks for a maximum of six cycles. Close cardiac monitoring was implemented in the study design.


RESULTS
Congestive heart failure (CHF) occurred in three patients in the AT arm and in one patient in the AC arm (P = 0.62). Decreases in left ventricular ejection fraction to below the limit of normal were documented in 33% AT and 19% AC patients and were not predictive of CHF development.


CONCLUSIONS
AT is devoid of excessive cardiac risk among metastatic breast carcinoma patients, when the maximum planned cumulative dose of doxorubicin does not exceed 360 mg/m(2).
Biganzoli
Laura
L
IDBBC Unit, EORTC-IDBBC, Jules Bordet Institute, Boulevard de Waterloo 121, 7th floor, 1000 Brussels, Belgium. laura.biganzoli@bordet.be
Cufer
Tanja
T
Bruning
Peter
P
Coleman
Robert E
RE
Duchateau
Luc
L
Rapoport
Bernardo
B
Nooij
Marianne
M
Delhaye
François
F
Miles
D
D
Sulkes
Aaron
A
Hamilton
A
A
Piccart
Martine
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D012307:Risk Factors; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome
D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel