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Springerplus. 2016 Jun 30;5(1):947. doi: 10.1186/s40064-016-2457-1. eCollection 2016.

A randomized phase I trial of nanoparticle albumin-bound paclitaxel with or without mifepristone for advanced breast cancer.

Author information

1
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.
2
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637 USA.
3
Department of Health Studies, The University of Chicago, 5841 S. Maryland Ave., MC 2000, Chicago, IL 60637 USA.
4
Northshore University Health Systems, 2650 Ridge Ave # 4805, Evanston, IL 60201 USA.
5
Department of Pathology, The University of Chicago, 5841 S Maryland Ave., MC 6101, Chicago, IL USA.
6
Section of Endocrinology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 1027, Chicago, IL 60637 USA.

Abstract

PURPOSE:

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.

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