title: A randomized phase I trial of nanoparticle albumin-bound paclitaxel with or without mifepristone for advanced breast cancer.
abstract: OBJECTIVE
  Glucocorticoid receptor (GR) overexpression is associated with poor prognosis ER-negative breast cancer. GR antagonism with mifepristone increases chemotherapy-induced breast cancer cell death, therefore we conducted a phase I clinical trial of mifepristone and nab-paclitaxel in advanced breast cancer.
  
  
  METHODS
  A novel randomized phase I design was used to assess the effect of mifepristone on nab-paclitaxel pharmacokinetics and toxicity. Patients were randomized to placebo or mifepristone for the first cycle; mifepristone was given to all for subsequent cycles.
  
  
  RESULTS
  Nine patients were enrolled. All were found to have a twofold or greater increase in serum cortisol after mifepristone administration, reflecting effective GR inhibition. Neutropenia occurred at both nab-paclitaxel dose levels studied (100 and 80 mg/m(2)), and was easily managed with dose reduction and/or growth factor administration. Pharmacokinetic data suggest an interaction between nab-paclitaxel and mifepristone in some patients. Two patients had complete responses (CR), three partial responses (PR), one stable disease (SD), and three progressive disease (PD). Immunohistochemical staining for GR found six of nine tumors were GR-positive. All six GR-positive tumors were triple-negative at the time of recurrence. Of these six patients, two had CRs, two PRs, one SD, and one PD.
  
  
  CONCLUSIONS
  GR appears to be a promising target in TNBC, and GR inhibition plus chemotherapy produces manageable toxicity. While neutropenia was observed in some, a nab-paclitaxel dose of 100 mg/m(2) plus mifepristone 300 mg was found to be tolerable, and a randomized phase II trial of nab-paclitaxel with/without mifepristone is planned in GR-positive advanced TNBC.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA ; 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637-1470 USA.
authors.forename: Rita
authors.identifier: 0000-0001-5248-0876
authors.initials: R
authors.lastname: Nanda
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Stringer-Reasor
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Poornima
authors.initials: P
authors.lastname: Saha
authors.affiliation: Department of Health Studies, The University of Chicago, 5841 S. Maryland Ave., MC 2000, Chicago, IL 60637 USA.
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Libao
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hoffman
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Obeid
authors.affiliation: Northshore University Health Systems, 2650 Ridge Ave # 4805, Evanston, IL 60201 USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Merkel
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Khramtsova
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Skor
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S Maryland Ave., MC 6101, Chicago, IL USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.affiliation: Section of Endocrinology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 1027, Chicago, IL 60637 USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Cohen
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
authors.forename: Suzanne D
authors.initials: SD
authors.lastname: Conzen