Cardiac safety of trastuzumab in combination with epirubicin and cyclophosphamide in women with metastatic breast cancer: results of a phase I trial.
This prospective, parallel-group, dose-escalation study evaluated the cardiac safety of trastuzumab (Herceptin) plus epirubicin/cyclophosphamide (EC) in women with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) and determined an epirubicin dose for further evaluation. HER2-positive patients received standard-dose trastuzumab plus epirubicin (60 or 90 mg/m(2))/cyclophosphamide (600 mg/m(2)) 3-weekly (EC60+H, n=26; EC90+H, n=25), for four to six cycles; 23 HER2-negative patients received EC alone (90/600 mg/m(2)) 3-weekly for six cycles (EC90). All patients underwent thorough cardiac evaluation. Two EC90+H-treated patients experienced symptomatic congestive heart failure 4.5 and 6 months after the end of chemotherapy. One EC60+H-treated patient experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) to <50% 6 months after the end of chemotherapy. No such events occurred in control patients. Asymptomatic LVEF decreases of >10% points were detected in 12 (48%), 14 (56%) and 5 (24%) patients treated with EC60+H, EC90+H, and EC90. Objective response rates with EC60+H and EC90+H were >60%, and 26% for EC90 alone. These results indicate that trastuzumab may be combined with EC with manageable cardiotoxicity and promising efficacy.
Untch
M
M
Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde, Ludwig-Maximilians-Universität, München, Germany.
Eidtmann
H
H
du Bois
A
A
Meerpohl
H G
HG
Thomssen
Ch
Ch
Ebert
A
A
Harbeck
N
N
Jackisch
C
C
Heilman
V
V
Emons
G
G
Wallwiener
D
D
Wiese
W
W
Blohmer
J-U
JU
Höffken
K
K
Kuhn
W
W
Reichardt
P
P
Muscholl
M
M
Pauschinger
M
M
Langer
B
B
Lück
H J
HJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D018734:Genes, erbB-2; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011446:Prospective Studies; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015251:Epirubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab