title: A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer.
abstract: OBJECTIVE
  To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC).
  
  
  METHODS
  The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF).
  
  
  RESULTS
  The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to <50%, with a decrease from baseline>15%. LVEF median values remained stable from baseline to the end of the study (60%).
  
  
  CONCLUSIONS
  The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy. direzione.scientifica@irst.emr.it
authors.forename: D
authors.initials: D
authors.lastname: Amadori
authors.forename: C
authors.initials: C
authors.lastname: Milandri
authors.forename: G
authors.initials: G
authors.lastname: Comella
authors.forename: S
authors.initials: S
authors.lastname: Saracchini
authors.forename: S
authors.initials: S
authors.lastname: Salvagni
authors.forename: C
authors.initials: C
authors.lastname: Barone
authors.forename: R
authors.initials: R
authors.lastname: Bordonaro
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: A
authors.initials: A
authors.lastname: Barbato
authors.forename: P
authors.initials: P
authors.lastname: Serra
authors.forename: D
authors.initials: D
authors.lastname: Gattuso
authors.forename: O
authors.initials: O
authors.lastname: Nanni
authors.forename: B
authors.initials: B
authors.lastname: Baconnet
authors.forename: G
authors.initials: G
authors.lastname: Gasparini
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077143:Docetaxel; D004317:Doxorubicin; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human