title: Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study.
abstract: OBJECTIVE
  To determine the recommended dose, cardiac safety, and antitumor activity of nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and the anti-HER-2 monoclonal antibody trastuzumab in patients with HER-2-overexpressing locally advanced nonoperable breast cancer (LABC) and metastatic breast cancer (MBC).
  
  
  METHODS
  Women with measurable, previously untreated, HER-2-overexpressing LABC and MBC with a baseline left ventricular ejection fraction (LVEF) >50% received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and TLC-D99 every 3 weeks for 6 cycles. LVEF monitoring was done every 3 weeks for the first 18 weeks and every 8 weeks thereafter.
  
  
  RESULTS
  Sixty-nine patients participated, 15 in the dose escalating part and 54 at the recommended phase II dose (28 patients with LABC and 26 patients with MBC). The recommended doses of TLC-D99 and paclitaxel were 50 mg/m(2) every 3 weeks and 80 mg/m(2)/wk, respectively. Twelve (17%) patients developed asymptomatic declines in LVEF. In 8 of these patients, LVEF recovered to >or=50% after a median time of 9 weeks (range, 3-38 weeks). In the rest of patients, LVEF ranged from 44% to 49%. No patients developed symptomatic cardiac heart failure. The overall response rate was 98.1% (95% confidence interval, 90.1-99.9) with a median time to progression not reached in LABC and of 22.1 months (95% confidence interval, 16.4-46.3) in MBC patients.
  
  
  CONCLUSIONS
  Nonpegylated doxorubicin, paclitaxel, and trastuzumab combination is safe, does not result in clinically manifest cardiac toxicity, and has a high rate of durable responses in HER-2-overexpressing breast cancer patients. Further exploration of this combination is warranted.
authors.affiliation: Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Climent
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortés-Funes
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Pere
authors.initials: P
authors.lastname: Gascón
authors.forename: José I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Miguel
authors.initials: M
authors.lastname: Gil
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides
authors.forename: Lluís
authors.initials: L
authors.lastname: Cirera
authors.forename: Belén
authors.initials: B
authors.lastname: Ojeda
authors.forename: César A
authors.initials: CA
authors.lastname: Rodríguez
authors.forename: José M
authors.initials: JM
authors.lastname: Trigo
authors.forename: Josep
authors.initials: J
authors.lastname: Vazquez
authors.forename: Pilar
authors.initials: P
authors.lastname: Regueiro
authors.forename: Juan F
authors.initials: JF
authors.lastname: Dorado
authors.forename: José
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D018734:Genes, erbB-2; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects*; D000068878:Trastuzumab; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D000068878:Trastuzumab; D017239:Paclitaxel