TY - JOUR
T1 - Enzalutamide
T2 - A novel antiandrogen for patients with castrate-resistant prostate cancer
AU - Hoffman-Censits, Jean
AU - Kelly, Wm Kevin
PY - 2013/3/15
Y1 - 2013/3/15
N2 - Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo inmen with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P < 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed.
AB - Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo inmen with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P < 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed.
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U2 - 10.1158/1078-0432.CCR-12-2910
DO - 10.1158/1078-0432.CCR-12-2910
M3 - Review article
C2 - 23300275
AN - SCOPUS:84875150133
SN - 1078-0432
VL - 19
SP - 1335
EP - 1339
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -