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Clin Cancer Res. 2017 May 1;23(9):2169-2176. doi: 10.1158/1078-0432.CCR-16-1357. Epub 2016 Nov 9.

Neoadjuvant Enzalutamide Prior to Prostatectomy.

Author information

1
Department of Medicine, University of Washington, Seattle, Washington. rbmontgo@uw.edu.
2
Department of Pathology, University of Washington, Seattle, Washington.
3
Princess Margaret Cancer Centre, Toronto, Canada.
4
Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.
5
Beth Israel Deaconess Medical Center, Boston, Massachusetts.
6
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
7
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
8
BC Cancer Agency and University of British Columbia, Vancouver, Canada.
9
Department of Urology, University of Washington, Seattle, Washington.
10
Department of Urology, Emory University, Atlanta, Georgia.
11
Medivation, Inc., San Francisco, California.
12
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
13
Memorial Sloan Kettering Cancer Center, New York, New York.
14
Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, and Department of Medicine, Division of Gerontology & Geriatric Medicine, University of Washington, Seattle, Washington.
15
Department of Medicine, University of Washington, Seattle, Washington.
16
Brigham and Women's Hospital, Boston, Massachusetts.
17
Astellas Pharma, Inc., Northbrook, Illinois.

Abstract

Purpose: Prostate cancer is dependent on androgen receptor (AR) activation. Optimal AR antagonism may effectively cytoreduce local disease and suppress or eliminate micrometastases. We evaluated neoadjuvant therapy prior to prostatectomy with the potent AR antagonist enzalutamide (enza) either alone or in combination with dutasteride (dut) and leuprolide (enza/dut/luteinizing hormone-releasing hormone analogues [LHRHa]).Experimental Design: Forty-eight of 52 men with intermediate or high-risk localized prostate cancer proceeded to prostatectomy after neoadjuvant enzalutamide or enza/dut/LHRHa for 6 months. We assessed pathologic complete response (pCR), minimal residual disease (MRD; ≤3 mm maximum diameter of residual disease), residual cancer burden (RCB), and expression of PSA and serum and tissue androgen concentrations. We compared the proportion of patients with pCR in each treatment arm with a historical control rate of 5%, based on previous reports of flutamide with LHRHa.Results: In the enzalutamide arm, none of the 25 patients achieved pCR or MRD. In the enza/dut/LHRHa arm, one of 23 patients (4.3%) achieved pCR and 3 of 23 (13.0%) achieved MRD. Median RCB was higher in the enzalutamide arm than in the enza/dut/LHRHa arm (0.41 cm3 vs. 0.06 cm3, respectively). Tissue testosterone and dihydrotestosterone levels correlated with RCB. No adverse events leading to study drug discontinuation were reported.Conclusions: Combination therapy with enza/dut/LHRHa resulted in pCR and MRD rates comparable with historical controls. Evidence of continued AR activity in residual tumor suggests that AR signaling may contribute to survival. Strategies to more effectively ablate AR activity are warranted to determine whether more substantial antitumor effects are observed. Clin Cancer Res; 23(9); 2169-76. ©2016 AACR.

PMID:
28151719
PMCID:
PMC5570479
DOI:
10.1158/1078-0432.CCR-16-1357
[Indexed for MEDLINE]
Free PMC Article

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