title: Phase II study of bortezomib and pegylated liposomal doxorubicin in the treatment of metastatic breast cancer.
abstract: BACKGROUND
  Based on preclinical studies and a phase I trial of the combination of bortezomib and pegylated liposomal doxorubicin (PLD), which both showed activity in breast cancer, we conducted a phase II study of this regimen in patients with metastatic breast cancer.
  
  
  METHODS
  Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every-21-day cycle, along with PLD 30 mg/m2 on day 4. The primary objective was to evaluate the response rate of this combination, while secondary objectives were to obtain further safety data about this combination, to evaluate the time to disease progression (TTP), and to evaluate response by the breast cancer subtype.
  
  
  RESULTS
  One of 12 evaluable patients had a partial response (8%), while 3 (25%) had stable disease. At 26 months follow-up, the median overall survival was 4.3 months (95% CI, 1.2-26.2) and the median TTP was 1.3 months (95% CI, 0.8-14.0 months). The combination was well tolerated, with the most common events including low-grade nausea and vomiting, neutropenia, and neuropathy, and no cardiac toxicity was seen. Of the 7 tumors subtyped, no association was seen between intrinsic subtype or receptor status and response.
  
  
  CONCLUSIONS
  The combination of PLD and bortezomib was well tolerated but has minimal activity in heavily pretreated unselected metastatic breast cancer.
authors.affiliation: The Lineberger Comprehensive Cancer Center, and Division of Hematology/Oncology, School of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive, Chapel Hill, NC 27599, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Irvin
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Wing-Keung
authors.initials: WK
authors.lastname: Chiu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.forename: Frances A
authors.initials: FA
authors.lastname: Collichio
authors.forename: Philip S
authors.initials: PS
authors.lastname: Bernard
authors.forename: Inge J
authors.initials: IJ
authors.lastname: Stijleman
authors.forename: Charles
authors.initials: C
authors.lastname: Perou
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D004317:Doxorubicin