title: Phase II trial of combination of pegylated liposomal doxorubicin, cisplatin, and infusional 5-fluorouracil (CCF) plus trastuzumab as preoperative treatment for locally advanced and inflammatory breast cancer.
abstract: BACKGROUND
  Pegylated liposomal doxorubicin (PLD) was shown as active but less toxic compared to doxorubicin in advanced breast cancer. Given its low cardiotoxicity, the combination of PLD and trastuzumab appears most attractive in the treatment of human epidermal factor receptor 2 (HER2)-positive breast cancer.
  
  
  METHODS
  We investigated the activity of 8 courses of PLD in combination with cisplatin and infusional 5-fluorouracil (CCF) plus 3-week trastuzumab in patients with primary or recurrent cT2-T4 a-d, N0-3, M0 any estrogen receptor (ER), HER2-positive breast cancer. Patients with ER and/or progesterone receptor (PgR) ≥ 10% tumors received also letrozole (plus triptorelin if premenopausal). The principal endpoint was clinical response rate; secondary endpoints were the pathologic complete response rate (pCR) and the cardiac safety of the combination.
  
  
  RESULTS
  Thirty-two patients were enrolled in the study and all are evaluable for response and toxicity. Fifteen patients (47%) had ER-positive tumors, 15 patients and 2 patients had ER absent and ER poor tumors, respectively. Thirteen patients (41%) had inflammatory breast cancer (IBC) and 84% of patients had clinically positive nodes. A clinical response rate of 94% (95% CI, 79%-99%) and a pCR rate of 41% (95% CI, 24%-59%) were observed. Fifty-four percent of patients with IBC obtained a pCR. Eleven patients discontinued treatment before completing 8 courses as planned. No patient developed relevant cardiac toxicity.
  
  
  CONCLUSIONS
  In this series of very locally advanced breast cancer, the combination of CCF and trastuzumab was very active obtaining an impressive rate of pCR, particularly in IBC, which merits further investigation in larger series.
authors.affiliation: Research Unit of Medical Senology, European Institute of Oncology, Milan, Italy. Rosalba.torrisi@humanitas.it
authors.forename: Rosalba
authors.initials: R
authors.lastname: Torrisi
authors.forename: Anna
authors.initials: A
authors.lastname: Cardillo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cancello
authors.forename: Silvia
authors.initials: S
authors.lastname: Dellapasqua
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduzzi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ghisini
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Paolo
authors.initials: P
authors.lastname: Veronesi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011300:Preoperative Care; D011960:Receptors, Estrogen / Q000032:analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000068878:Trastuzumab; D002945:Cisplatin; D005472:Fluorouracil