Online citations, reference lists, and bibliographies.
← Back to Search

Cardiac Safety Of Trastuzumab In Combination With Epirubicin And Cyclophosphamide In Women With Metastatic Breast Cancer: Results Of A Phase I Trial.

M. Untch, H. Eidtmann, A. Du Bois, H. G. Meerpohl, C. Thomssen, A. Ebert, N. Harbeck, C. Jackisch, V. Heilman, G. Emons, D. Wallwiener, W. Wiese, J. Blohmer, K. Hoeffken, W. Kuhn, P. Reichardt, M. Muscholl, M. Pauschinger, B. Langer, H. Lueck
Published 2004 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
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.
This paper references
10.1200/JCO.2002.20.5.1156
Cardiac dysfunction in the trastuzumab clinical experience.
J. Speyer (2002)
10.1073/PNAS.89.10.4285
Humanization of an anti-p185HER2 antibody for human cancer therapy.
P. Carter (1992)
10.1093/JNCI/DJH198
Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer.
G. Konecny (2004)
10.2165/00003495-199345050-00011
Epirubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cancer chemotherapy.
G. Plosker (1993)
10.1126/SCIENCE.3798106
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
10.1126/SCIENCE.2992089
Amplification of a novel v-erbB-related gene in a human mammary carcinoma.
C. R. King (1985)
10.1126/SCIENCE.2470152
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
10.1093/JNCI/92.24.1991
HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15.
S. Paik (2000)
HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil.
A. Di Leo (2002)
10.1200/JCO.1992.10.4.599
HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.
D. Allred (1992)
10.1126/SCIENCE.3012781
The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity.
T. Akiyama (1986)
10.1002/stem.160413
The HER‐2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy
Jeffrey S. Ross (1998)
10.1159/000066197
The Future of Targeted Therapy: Combining Novel Agents
L. Gianni (2002)
10.1126/SCIENCE.2999974
Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
L. Coussens (1985)
10.1016/0033-0620(91)90022-E
Cardiovascular sequelae of therapeutic thoracic radiation.
M. Arsenian (1991)
10.1200/JCO.20.3.719
Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.
C. Vogel (2002)
10.1007/BF01961241
Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu
C. Benz (2005)
10.1016/0046-8177(92)90257-4
Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer.
D. Allred (1992)
10.1056/NEJM200103153441101
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.
D. Slamon (2001)
10.1200/JCO.1999.17.9.2639
Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.
M. Cobleigh (1999)
10.1016/S0959-8049(02)00745-1
Topoisomerase II-alpha (topoII) and HER2 amplification in breast cancers and response to preoperative doxorubicin chemotherapy.
K. Park (2003)
10.1200/JCO.2002.20.5.1215
Cardiac dysfunction in the trastuzumab clinical trials experience.
A. Seidman (2002)



This paper is referenced by
10.3816/CBC.2009.n.019
Phase I study of nonpegylated liposomal doxorubicin plus trastuzumab in patients with HER2-positive breast cancer.
M. Theodoulou (2009)
10.1007/s10549-005-9030-x
Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer
M. Venturini (2005)
10.1016/j.cardfail.2008.02.002
Trastuzumab-induced cardiomyopathy.
M. Guglin (2008)
10.2165/00003495-200767050-00002
Oral Vinorelbine
M. Aapro (2012)
10.1056/NEJMOA053028
Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.
H. Joensuu (2006)
Cardiotoxicity of Non-Cardiovascular Drugs
G. Minotti (2010)
10.1158/0008-5472.CAN-05-1161
Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice.
M. Tabuchi (2005)
10.1007/978-3-642-12681-9_19
Systemische Therapie des metastasierten Mammakarzinoms
Hans-Joachiam Lück (2010)
10.1007/2-287-31109-2_12
Cancers du sein avec HER2 surexprimé : quoi de neuf dans la prise en charge clinique ?
H. Roché (2006)
10.1159/000092645
Trastuzumab (Herceptin®): Monoclonal Antibody in the Treatment of HER2/neu-Overexpressing Breast Cancer in the Metastatic and (Neo)adjuvant Situation
N. Ditsch (2006)
10.1634/theoncologist.2008-0137
Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations.
M. Martín (2009)
10.1007/978-1-59745-337-0_14
Targeted Therapy For Breast Cancer
D. Atieh (2008)
10.6000/1929-2279.2012.01.01.14
Present and Emerging Targeted Therapy for Metastatic Breast Cancer
Vito Lorusso (2012)
10.1200/JCO.2009.21.9709
First-line trastuzumab plus epirubicin and cyclophosphamide therapy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: cardiac safety and efficacy data from the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) trial.
M. Untch (2010)
10.1053/J.SEMINONCOL.2004.07.020
Maximizing clinical benefit with trastuzumab.
R. Bell (2004)
10.1002/9780470660379.CH5
Cardiovascular Toxicity of Antitumor Drugs: Dimension of the Problem in Adult Settings
J. Carver (2010)
10.1093/ANNONC/MDL476
A review of the use of trastuzumab (Herceptin) plus vinorelbine in metastatic breast cancer.
A. Chan (2007)
10.1007/s12282-009-0142-8
The role of trastuzumab in the management of HER2-positive metastatic breast cancer: an updated review
Y. Tokuda (2009)
10.1093/annonc/mdn292
Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies.
D. Rayson (2008)
10.1053/J.SEMINONCOL.2004.07.019
Optimizing treatment of HER2-positive metastatic breast cancer.
A. Jones (2004)
10.1007/s00280-005-0116-2
Pegylated liposomal doxorubicin in combination with gemcitabine: a phase II study in anthracycline-naïve and anthracycline pretreated metastatic breast cancer patients
A. Fabi (2005)
Review Article Trastuzumab-Induced Cardiomyopathy
M. Guglin (2008)
10.2165/00003495-200666120-00004
Monoclonal Antibody-Based Targeted Therapy in Breast Cancer
C. Bernard-Marty (2012)
10.1007/s00392-011-0406-0
Echocardiography signs of early cardiac impairment in patients with breast cancer and trastuzumab therapy
S. Lange (2011)
10.1186/1755-8794-3-17
Predicting environmental chemical factors associated with disease-related gene expression data
C. Patel (2009)
10.1093/ANNONC/MDM217
Safety and activity of trastuzumab-containing therapies for the treatment of metastatic breast cancer: our long-term clinical experience (GOIM study).
V. Adamo (2007)
10.1021/tx800002r
Cardiotoxicity of antitumor drugs.
P. Menna (2008)
10.1016/B978-1-4377-1015-1.00009-6
9 – Management of cardiac and pulmonary treatment–related side effects
Joseph R. Carver (2011)
10.2741/s249
Which role for EGFR therapy in breast cancer?
V. Lorusso (2012)
10.1007/s00761-006-1120-9
Immunologische Therapie beim Mammakarzinom
N. Ditsch (2006)
10.1007/978-2-287-71478-8_46
Cardiotoxicité des anthracyclines dans le contexte du cancer du sein métastasé. Où en sommes-nous ? Comment progresser ?
E. Ferrari (2007)
10.1007/s10147-014-0727-x
Efficacy and safety of neoadjuvant chemotherapy with concurrent liposomal-encapsulated doxorubicin, paclitaxel and trastuzumab for human epidermal growth factor receptor 2-positive breast cancer in clinical practice
J. Gavilá (2014)
See more
Semantic Scholar Logo Some data provided by SemanticScholar