title: Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2-overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels.
  
  
  METHODS
  Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m(2)/wk and trastuzumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuzumab 4 mg/kg was administered 1 day before the start of the first cycle.
  
  
  RESULTS
  The median delivered dose-intensity of docetaxel was 24 mg/m(2)/wk (range, 18 to 27 mg/m(2)/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [CI], 44% to 80%). The ORR in patients whose tumors were HER-2-positive by fluorescence in situ hybridization was 67% (16 of 24 patients; 95% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 7% to 70%) in patients with low HER-2 ECD levels (P =.04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing.
  
  
  CONCLUSIONS
  Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2-overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. festeva@mdanderson.org
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Daniel
authors.initials: D
authors.lastname: Booser
authors.forename: Laura T
authors.initials: LT
authors.lastname: Guerra
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Bita
authors.initials: B
authors.lastname: Esmaeli
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Fritsche
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D043823:Taxoids; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D000077143:Docetaxel; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab