title: Cardiac safety of trastuzumab in combination with epirubicin and cyclophosphamide in women with metastatic breast cancer: results of a phase I trial.
abstract: 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.
authors.affiliation: Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.forename: H
authors.initials: H
authors.lastname: Eidtmann
authors.forename: A
authors.initials: A
authors.lastname: du Bois
authors.forename: H G
authors.initials: HG
authors.lastname: Meerpohl
authors.forename: Ch
authors.initials: Ch
authors.lastname: Thomssen
authors.forename: A
authors.initials: A
authors.lastname: Ebert
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
authors.forename: C
authors.initials: C
authors.lastname: Jackisch
authors.forename: V
authors.initials: V
authors.lastname: Heilman
authors.forename: G
authors.initials: G
authors.lastname: Emons
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
authors.forename: W
authors.initials: W
authors.lastname: Wiese
authors.forename: J-U
authors.initials: JU
authors.lastname: Blohmer
authors.forename: K
authors.initials: K
authors.lastname: Höffken
authors.forename: W
authors.initials: W
authors.lastname: Kuhn
authors.forename: P
authors.initials: P
authors.lastname: Reichardt
authors.forename: M
authors.initials: M
authors.lastname: Muscholl
authors.forename: M
authors.initials: M
authors.lastname: Pauschinger
authors.forename: B
authors.initials: B
authors.lastname: Langer
authors.forename: H J
authors.initials: HJ
authors.lastname: Lück
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015251:Epirubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab