title: Anthracycline and trastuzumab in breast cancer treatment.
abstract: This study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastatic breast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) in comparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those with metastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapy for metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, open-label, phase I study in Germany. A control group of 23 patients received EC 90/600 mg/m2 3-weekly for six cycles (EC90 alone). A total of 26 HER2-positive patients were treated with trastuzumab, or H (2 mg/kg weekly after an initial loading dose of 4 mg/kg), and EC 60/600 mg/m2 3-weekly for six cycles (EC60+H); another 25 HER2-positive patients received H and EC 90/600 mg/m2 3-weekly for six cycles. Asymptomatic reductions in left ventricular ejection fraction (LVEF) of more than 10% points were detected in 12 patients (48%) treated with EC60+H and in 14 patients (56%) treated with EC90+H vs 6 patients (26%) in the EC90 alone cohort. LVEF decreases to <50% occurred in one patient in the EC60+H cohort and in two patients in the EC90+H cohort during the H monotherapy. No cardiac event occurred in the cohort with EC90 alone. The overall response rates for EC60+H and EC90+H were >60%, vs 26% for EC90 alone. The interim results of this study approve the cardiac safety of the combination of H with EC, with low risk of cardiac toxicity. The combination regimen revealed promising efficacy.
authors.affiliation: Klinikum Grosshadern, Frauenklinik München, Ludwig-Maximilians-Universität, München, Germany. mwolf@med.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.forename: I
authors.initials: I
authors.lastname: Himsl
authors.forename: S
authors.initials: S
authors.lastname: Kahlert
authors.forename: H J
authors.initials: HJ
authors.lastname: Lueck
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: C
authors.initials: C
authors.lastname: Thomssen
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
authors.forename: C
authors.initials: C
authors.lastname: Jackisch
authors.forename: R
authors.initials: R
authors.lastname: Kreienberg
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: G
authors.initials: G
authors.lastname: Schaller
authors.forename: W
authors.initials: W
authors.lastname: Kuhn
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
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005858:Germany; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab