title: Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer.
abstract: BACKGROUND
  A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2.
  
  
  METHODS
  Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD).
  
  
  RESULTS
  Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035).
  
  
  CONCLUSIONS
  Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.
authors.affiliation: Medical Oncology Division, San Filippo Neri Hospital, Unità Operativa Complessa di Oncologia Medica, Azienda Complesso Ospedaliero di Rilevanza Nazionale S. Filippo Neri , Via G. Martinotti, 20-00135 Rome, Italy. gasparini.oncology@tiscalinet.it
authors.forename: Giampietro
authors.initials: G
authors.lastname: Gasparini
authors.forename: Massimo
authors.initials: M
authors.lastname: Gion
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Paola
authors.initials: P
authors.lastname: Papaldo
authors.forename: Diana
authors.initials: D
authors.lastname: Crivellari
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Filippelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Vittorio
authors.initials: V
authors.lastname: Silingardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Torino
authors.forename: Antonella
authors.initials: A
authors.lastname: Spada
authors.forename: Matelda
authors.initials: M
authors.lastname: Zancan
authors.forename: Livia
authors.initials: L
authors.lastname: De Sio
authors.forename: Antonio
authors.initials: A
authors.lastname: Caputo
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Lambiase
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000556:secondary; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab