title: Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer.
abstract: BACKGROUND
  Preclinical data indicate that docetaxel, platinum salts, and the combination of both drugs are highly synergistic with the anti-HER2 antibody trastuzumab. The University of California at Los Angeles-Oncology Research Network (UCLA-ORN) and the Breast Cancer International Research Group (BCIRG) have conducted two phase II studies to evaluate docetaxel and trastuzumab in combination with either cisplatin or carboplatin for the treatment of women with advanced breast cancer that overexpresses HER2.
  
  
  METHODS
  Each study enrolled 62 patients with HER2-overexpressing tumors. Patients received a median of six cycles of docetaxel at 75 mg/m2 of body surface area and cisplatin (BCIRG 101 study) at 75 mg/m2 or carboplatin (UCLA-ORN study) at AUC = 6 mg/mL. min given on day 1 and then every 21 days. Trastuzumab was given on day 1, cycle 1 (4 mg/kg) and then continued weekly at 2 mg/kg for 1 year or until disease progression. Tumor measurements were obtained at baseline, after three cycles of chemotherapy, and then every 3 months. HER2 gene amplification was determined by fluorescence in situ hybridization.
  
  
  RESULTS
  Patient characteristics were comparable between trials with the exception that 15% of the patients in the UCLA-ORN study had received previous adjuvant taxane therapy. Both regimens were well tolerated, with manageable toxicities. Hematologic toxicities were more frequent in patients in the UCLA-ORN study than in patients in the BCIRG 101 study, whereas the reverse pattern was observed for non-hematologic toxicities. One patient in each study developed reversible congestive heart failure. Responses were observed in 49 of 62 patients in the BCIRG 101 study (overall response rate = 79%, 95% confidence interval [CI] = 66% to 89%) and in 34 of 59 evaluable patients in the UCLA-ORN study (overall response rate = 58%, 95% CI = 44% to 70%). Median times to progression were 9.9 months (95% CI = 8.3 to 13.1 months) and 12.7 months (95% CI = 8.6 to 15.5 months) for patients in the BCIRG 101 and UCLA-ORN studies, respectively. Overall response rates were higher and median time to progression was longer in the subset of patients whose tumors harbored HER2 gene amplification.
  
  
  CONCLUSIONS
  Combinations of docetaxel, a platinum salt, and trastuzumab are feasible and active in patients with advanced breast cancers that overexpress HER2. The BCIRG is conducting ongoing randomized studies of the three-drug combination in both the metastatic and adjuvant settings.
authors.affiliation: Oncology Research Network, David Geffen School of Medicine, and Division of Hematology/Oncology, University of California, Los Angeles 90095-7077, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pegram
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Donald W
authors.initials: DW
authors.lastname: Northfelt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Eleonor
authors.initials: E
authors.lastname: Quan
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Deborah
authors.initials: D
authors.lastname: Toppmeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Smylie
authors.forename: Alessandro
authors.initials: A
authors.lastname: Riva
authors.forename: Sandra
authors.initials: S
authors.lastname: Blitz
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: David
authors.initials: D
authors.lastname: Reese
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Lindsay
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
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*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D017671:Platinum Compounds / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012107:Research Design; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000077143:Docetaxel; D017671:Platinum Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab