Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling which blocks androgen-receptor interaction; inhibits translocation of the androgen receptor to the nucleus; impairs androgen receptor binding to DNA; and inhibits co-activator recruitment and receptor mediated DNA transcription.
In a Phase III randomized study comparing Enzalutamide to placebo in men 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, hazard ratio 0.63, p< 0.001). In addition, all secondary endpoints including proportion of patients with 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 which very potently blocks the androgen signaling pathway that is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials which led to its approval by the FDA in September of 2012 will be reviewed.
Written by:
Hoffman-Censits J, Kelly WK. Are you the author?
Medical Oncology, Thomas Jefferson University, Kimmel Cancer Center.
Reference: Clin Cancer Res. 2013 Jan 8. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-12-2910
PubMed Abstract
PMID: 23300275
