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Eur Urol. 2015 Nov;68(5):795-801. doi: 10.1016/j.eururo.2015.01.026. Epub 2015 Feb 16.

Long-term Safety and Antitumor Activity in the Phase 1-2 Study of Enzalutamide in Pre- and Post-docetaxel Castration-Resistant Prostate Cancer.

Author information

1
University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: thigano@u.washington.edu.
2
Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA.
3
Dana-Farber Cancer Institute, Boston, MA, USA.
4
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
5
Medivation Inc., San Francisco, CA, USA.
6
Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Abstract

BACKGROUND:

Given that some patients with castration-resistant prostate cancer (CRPC) have shown extended responses to the androgen receptor inhibitor enzalutamide, long-term safety of this drug is of interest.

OBJECTIVE:

To evaluate the long-term safety and antitumor activity of enzalutamide in CRPC patients.

DESIGN, SETTING, AND PARTICIPANTS:

This phase 1-2 study evaluated enzalutamide in 140 CRPC patients with and without prior chemotherapy. Initial findings were published in 2010. We report updated results from an additional 17-mo follow-up for antitumor activity and >4 yr for safety.

INTERVENTION:

Patients received 30-600mg/d oral enzalutamide. During long-term dosing, all patients were switched first to the maximum tolerated dose of 240mg/d and then to the phase 3 dose of 160mg/d.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Safety was assessed regularly. The Kaplan-Meier method was used to estimate the distributions of time to prostate-specific antigen (PSA) progression and time to radiographic progression.

RESULTS AND LIMITATIONS:

The safety profile of enzalutamide was consistent over time, with little change in the rates of commonly reported adverse events (AEs) or the incidence of grade 3/4 AEs. Fatigue of any grade was the most common dose-dependent AE, experienced by 70% of patients, with 14% of patients reporting grade 3/4 fatigue. The median time to PSA progression was not reached for chemotherapy-naive patients and was 45 wk for postchemotherapy patients; the corresponding median time to radiographic progression was 56 wk and 25 wk.

CONCLUSIONS:

Enzalutamide showed durable antitumor activity in chemotherapy-naive and postchemotherapy patients, and was well tolerated, even in patients treated for 4 yr.

PATIENT SUMMARY:

Enzalutamide was active against prostate cancer and was well tolerated, even for up to 4 yr of treatment, supporting its potential for long-term use in men with prostate cancer. Fatigue was the most common side effect, occurring at varying degrees of severity in most patients.

KEYWORDS:

Androgen receptor inhibitor; Castration-resistant prostate cancer; Enzalutamide; Long-term follow-up; MDV3100; Tolerability

PMID:
25698064
PMCID:
PMC5013546
DOI:
10.1016/j.eururo.2015.01.026
[Indexed for MEDLINE]
Free PMC Article

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