title: Combination docetaxel and trastuzumab treatment for patients with HER-2-overexpressing metastatic breast cancer: a multicenter, phase-II study.
abstract: BACKGROUND
  Pre-clinical and clinical studies indicate that a combination of docetaxel and trastuzumab may effectively treat patients with human epidermal growth factor receptor-2 (HER-2) overexpressing metastatic breast cancer. We evaluated the efficacy and safety of this combination in a multicenter, open-label phase II study in Japan.
  
  
  METHODS
  Women with metastatic breast cancer whose tumors overexpressed HER-2, as assessed by immunohistochemistry and by fluorescence in situ hybridisation, received 2 to 6 cycles of docetaxel (70 mg/m2, every 3 weeks) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). The primary endpoint was tumor response. Secondary endpoints were time to disease progression and adverse events.
  
  
  RESULTS
  Of the 40 women enrolled in the study, 27 (68%) completed 6 cycles of treatment. Three patients discontinued the study before the second cycle. Median follow-up was 20.8 months (range, 0.6 to 30.9 months). The overall response rate was 65% (26/40; 95% CI, 48% to 79%). The median time to progression was 6.8 months (range, 0.6 to 21.2 months). Of the 40 patients, 35 (88%) had grade 3 or 4 leukopenia, and 33 (83%) had grade 3 or 4 neutropenia. Most instances of leukopenia and neutropenia were manageable by reducing the dose of docetaxel or by treatment with granulocyte colony-stimulating factor. In 4 patients, left ventricular ejection fraction decreased by more than 10% from baseline.
  
  
  CONCLUSIONS
  The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.
authors.affiliation: Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan. nobus@niigata-cc.jp
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sato
authors.forename: Muneaki
authors.initials: M
authors.lastname: Sano
authors.forename: Toshio
authors.initials: T
authors.lastname: Tabei
authors.forename: Taro
authors.initials: T
authors.lastname: Asaga
authors.forename: Jiro
authors.initials: J
authors.lastname: Ando
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Naohito
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Morihiko
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012142:Respiratory Tract Neoplasms / Q000556:secondary; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000556:secondary; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab