PMID- 12885806
OWN - NLM
STAT- MEDLINE
DCOM- 20030904
LR  - 20220310
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 21
IP  - 15
DP  - 2003 Aug 1
TI  - Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing 
      metastatic breast cancer: multicenter phase II trial with clinical outcomes, 
      analysis of serum tumor markers as predictive factors, and cardiac surveillance 
      algorithm.
PG  - 2889-95
AB  - PURPOSE: Trastuzumab-based therapy improves survival for women with human 
      epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We 
      conducted a multicenter phase II study to evaluate the efficacy and safety of 
      trastuzumab combined with vinorelbine, and to assess cardiac surveillance 
      algorithms and tumor markers as prognostic tools. PATIENTS AND METHODS: Patients 
      with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in 
      situ hybridization [FISH]-positive) metastatic breast cancer received first-line 
      chemotherapy with trastuzumab and vinorelbine to determine response rate. 
      Eligibility criteria were measurable disease and baseline ejection fraction >or= 
      50%. Serial testing for HER2 extracellular domain (ECD) was performed. RESULTS: 
      Fifty-four women from 17 participating centers were entered onto the study. The 
      overall response rate was 68% (95% confidence interval, 54% to 80%). Response 
      rates were not affected by method of HER2 status determination (FISH v IHC) or by 
      prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% 
      of patients were progression free after 1 year. Concurrent therapy was quite 
      feasible with maintained dose-intensity. Patients received both chemotherapy and 
      trastuzumab on 90% of scheduled treatment dates. Two patients experienced 
      cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart 
      failure. A surveillance algorithm of screening left ventricular ejection fraction 
      (LVEF) at 16 weeks successfully identified women at risk for experiencing 
      cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of 
      decline in HER2 ECD during cycle 1 predicted tumor progression. CONCLUSION: 
      Trastuzumab and vinorelbine constitute effective and well-tolerated first-line 
      treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF 
      can be observed with surveillance of LVEF at 16 weeks to identify those at risk 
      for cardiotoxicity.
FAU - Burstein, Harold J
AU  - Burstein HJ
AD  - Dana-Farber Cancer Institute, Brigham & Women's Hospital, Harvard Medical School, 
      Boston, MA 02115, USA. hburstein@partners.org.
FAU - Harris, Lyndsay N
AU  - Harris LN
FAU - Marcom, P Kelly
AU  - Marcom PK
FAU - Lambert-Falls, Rosemary
AU  - Lambert-Falls R
FAU - Havlin, Kathleen
AU  - Havlin K
FAU - Overmoyer, Beth
AU  - Overmoyer B
FAU - Friedlander, Robert J Jr
AU  - Friedlander RJ Jr
FAU - Gargiulo, Janet
AU  - Gargiulo J
FAU - Strenger, Rochelle
AU  - Strenger R
FAU - Vogel, Charles L
AU  - Vogel CL
FAU - Ryan, Paula D
AU  - Ryan PD
FAU - Ellis, Mathew J
AU  - Ellis MJ
FAU - Nunes, Raquel A
AU  - Nunes RA
FAU - Bunnell, Craig A
AU  - Bunnell CA
FAU - Campos, Susana M
AU  - Campos SM
FAU - Hallor, Michele
AU  - Hallor M
FAU - Gelman, Rebecca
AU  - Gelman R
FAU - Winer, Eric P
AU  - Winer EP
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers, Tumor)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - Q6C979R91Y (Vinorelbine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Algorithms
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Biomarkers, Tumor/blood
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Disease Progression
MH  - Female
MH  - Heart Diseases/chemically induced
MH  - Humans
MH  - Infusions, Intravenous
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - ROC Curve
MH  - Receptor, ErbB-2/*metabolism
MH  - Survival Analysis
MH  - Trastuzumab
MH  - Treatment Outcome
MH  - Vinblastine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Vinorelbine
EDAT- 2003/07/30 05:00
MHDA- 2003/09/05 05:00
CRDT- 2003/07/30 05:00
PHST- 2003/07/30 05:00 [pubmed]
PHST- 2003/09/05 05:00 [medline]
PHST- 2003/07/30 05:00 [entrez]
AID - JCO.2003.02.018 [pii]
AID - 10.1200/JCO.2003.02.018 [doi]
PST - ppublish
SO  - J Clin Oncol. 2003 Aug 1;21(15):2889-95. doi: 10.1200/JCO.2003.02.018.