Multicenter randomized phase III trial of epirubicin plus paclitaxel vs epirubicin followed by paclitaxel in metastatic breast cancer patients: focus on cardiac safety.
The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mg m(-2) plus Paclitaxel 200 mg m(-2) (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mg m(-2) on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mg m(-2) on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel.
Baldini
E
E
Medical Oncology Department, S. Chiara University-Hospital, Via Roma 67, 56132 Pisa, Italy. e.baldini@do.med.unipi.it
Prochilo
T
T
Salvadori
B
B
Bolognesi
A
A
Aldrighetti
D
D
Venturini
M
M
Rosso
R
R
Carnino
F
F
Gallo
L
L
Giannessi
P
P
Conte
P F
PF
Orlandini
C
C
Bruzzi
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left
D015251:Epirubicin; D017239:Paclitaxel