PMID- 25698064
OWN - NLM
STAT- MEDLINE
DCOM- 20160727
LR  - 20211203
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Print)
IS  - 0302-2838 (Linking)
VI  - 68
IP  - 5
DP  - 2015 Nov
TI  - Long-term Safety and Antitumor Activity in the Phase 1-2 Study of Enzalutamide in 
      Pre- and Post-docetaxel Castration-Resistant Prostate Cancer.
PG  - 795-801
LID - S0302-2838(15)00069-X [pii]
LID - 10.1016/j.eururo.2015.01.026 [doi]
AB  - 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.
CI  - Copyright (c) 2015. Published by Elsevier B.V.
FAU - Higano, Celestia S
AU  - Higano CS
AD  - University of Washington School of Medicine, Fred Hutchinson Cancer Research 
      Center, Seattle, WA, USA. Electronic address: thigano@u.washington.edu.
FAU - Beer, Tomasz M
AU  - Beer TM
AD  - Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA.
FAU - Taplin, Mary-Ellen
AU  - Taplin ME
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Efstathiou, Eleni
AU  - Efstathiou E
AD  - University of Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Hirmand, Mohammad
AU  - Hirmand M
AD  - Medivation Inc., San Francisco, CA, USA.
FAU - Forer, David
AU  - Forer D
AD  - Medivation Inc., San Francisco, CA, USA.
FAU - Scher, Howard I
AU  - Scher HI
AD  - 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.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150216
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Benzamides)
RN  - 0 (Nitriles)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - 2010-15-3 (Phenylthiohydantoin)
RN  - 93T0T9GKNU (enzalutamide)
RN  - EC 3.4.21.- (KLK3 protein, human)
RN  - EC 3.4.21.- (Kallikreins)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
CIN - Eur Urol. 2015 Nov;68(5):802-4. PMID: 25922192
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Androgen Receptor Antagonists/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Agents, Hormonal/therapeutic use
MH  - Benzamides
MH  - Bone Neoplasms/*drug therapy/secondary
MH  - Disease-Free Survival
MH  - Docetaxel
MH  - Humans
MH  - Kallikreins/blood
MH  - Lymph Nodes/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*blood
MH  - Nitriles
MH  - Phenylthiohydantoin/*analogs & derivatives/therapeutic use
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy/pathology
MH  - Taxoids/*therapeutic use
PMC - PMC5013546
MID - NIHMS810851
OTO - NOTNLM
OT  - Androgen receptor inhibitor
OT  - Castration-resistant prostate cancer
OT  - Enzalutamide
OT  - Long-term follow-up
OT  - MDV3100
OT  - Tolerability
EDAT- 2015/02/24 06:00
MHDA- 2016/07/28 06:00
PMCR- 2016/11/01
CRDT- 2015/02/21 06:00
PHST- 2014/10/21 00:00 [received]
PHST- 2015/01/26 00:00 [accepted]
PHST- 2015/02/21 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - S0302-2838(15)00069-X [pii]
AID - 10.1016/j.eururo.2015.01.026 [doi]
PST - ppublish
SO  - Eur Urol. 2015 Nov;68(5):795-801. doi: 10.1016/j.eururo.2015.01.026. Epub 2015 
      Feb 16.