title: Trastuzumab plus weekly epirubicin and paclitaxel for locally advanced and metastatic breast cancer: preliminary results of a feasibility-phase II study aimed at cardiotoxicity.
abstract: A feasibility-phase II study was conducted to assess the cardiotoxicity of weekly trastuzumab, epirubicin, and paclitaxel in patients with human epidermal growth factor receptor-2-positive metastatic breast cancer. Untreated patients with human epidermal growth factor receptor-2-positive advanced breast cancer received trastuzumab (day 1), and epirubicin (25 mg/m2) and paclitaxel (80 mg/m2) (day 2) on a weekly basis. The rate of patients with left-ventricular ejection fraction (L-VEF) reduction greater than 10% after 12 weeks was the primary end point. According to a two-stage model, an initial step with 15 patients was required; after 11 patients without toxicity, a second step with 21 patients was planned. After 255 courses in 15 patients (median treatment weeks: 18), the relative dose intensity was 94.7%. At 12 weeks, three patients (20%) displayed a L-VEF reduction greater than 10%, six and six (40%) patients showed a L-VEF reduction < or =10% or no change, respectively. Baseline, -12 weeks, and -24 weeks median L-VEF was 69% (range 61-77), 65% (range 60-76), and 65% (range 55-73), respectively. No EKG/cardiac signs were present. Thirteen patients had grade 3 alopecia and two patients had grade 3 asthenia, in the absence of severe hematological toxicity. Objective responses were observed in 11 patients (73.3%, 95% confidence interval 51.0-95.7), with 10 partial. The weekly administration of trastuzumab-epirubicin-paclitaxel is extremely tolerable, also with regard to L-VEF reduction. These results allowed entrance to the second step of the study.
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nisticò
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Vanja
authors.initials: V
authors.lastname: Vaccaro
authors.forename: Federica
authors.initials: F
authors.lastname: Cuppone
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Armando
authors.initials: A
authors.lastname: Carpino
authors.forename: Fiorentino
authors.initials: F
authors.lastname: Izzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Tropea
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015251:Epirubicin; D000068878:Trastuzumab; D017239:Paclitaxel