title: The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer.
abstract: OBJECTIVE
  Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzumab (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival.
  
  
  METHODS
  Patients with HER-2/neu immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)-amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of >or= 55% were enrolled, regardless of tumor size or nodal status. Treatment consisted of AC (60/600 mg/m(2)) x 4 followed by P (175 mg/m(2)) x 4 every 2-weekly with pegfilgrastim (6 mg on day 2) + T x1 year. LVEF by radionuclide scan was obtained at baseline, at months 2, 6, 9, and 18.
  
  
  RESULTS
  From January 2005 to November 2005, 70 patients were enrolled. The median age was 49 years (range, 27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2 in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in 67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70 patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients, it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was 28 months (range, 25 to 35 months). One patient (1%) experienced congestive heart failure (CHF). There were no cardiac deaths.
  
  
  CONCLUSIONS
  Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.
authors.affiliation: Department of Medicine, Memorial Sloan- Kettering Cancer Center, 1275 York Ave, Howard 713, New York, NY 10021, USA. dangc@mskcc.org
authors.forename: Chau
authors.initials: C
authors.lastname: Dang
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.forename: Steven
authors.initials: S
authors.lastname: Sugarman
authors.forename: Tiffany
authors.initials: T
authors.lastname: Troso-Sandoval
authors.forename: Diana
authors.initials: D
authors.lastname: Lake
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Andrew
authors.initials: A
authors.lastname: Seidman
authors.forename: Nancy
authors.initials: N
authors.lastname: Sklarin
authors.forename: Maura
authors.initials: M
authors.lastname: Dickler
authors.forename: Violante
authors.initials: V
authors.lastname: Currie
authors.forename: Theresa
authors.initials: T
authors.lastname: Gilewski
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Moynahan
authors.forename: Pamela
authors.initials: P
authors.lastname: Drullinsky
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Carolyn
authors.initials: C
authors.lastname: Wasserheit-Leiblich
authors.forename: Nancy
authors.initials: N
authors.lastname: Mills
authors.forename: Richard
authors.initials: R
authors.lastname: Steingart
authors.forename: Katherine
authors.initials: K
authors.lastname: Panageas
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005784:Gene Amplification; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab