Enzalutamide in castration resistant prostate cancer

Androgen deprivation therapy is part of the initial treatment of patients with metastatic prostate cancer. Nevertheless, after an initial response and despite maintaining an effective testosterone suppression, the tumor is able to continue growing. Enzalutamide is an oral second generation pure antiandrogen that acts at various levels in the signal activation cascade of the androgen receptor and has demonstrated being effective in this phase of the disease. In the clinical trials completed, it has demonstrated benefits in overall patient survival in patients with the diagnosis of metastatic castration resistant prostate cancer. Recent studies have also demonstrated benefits in progression free survival in patients with non-metastatic castration resistant prostate cancer. Enzalutamide has an excellent toxicity profile, but we have to avoid it in patients with history of seizure episodes, mainly if they are under anti-epileptic drug therapy. Enzalutamide is rapidly metabolized by the liver, mainly through the CYP2C8 and to a lesser extent by CYP3A4/5 so that its metabolism may be altered when cytochrome isoenzyme inductor or inhibitor drugs are given concomitantly. Moreover, enzalutamide may require dose adjustment for other drugs since it is a potent inductor of CYP3A4 and a moderate inductor of CYP2C9 y el CYP2C19. Even though treatment with enzalutamide has significantly altered the natural history of the disease, in most cases it will progress by development of resistance mechanisms, among which we may emphasize androgen receptor mutations, overexpression, amplification and variants, as well as the intracrine production of androgens. Enzalutamide must be considered as first line therapy in patients with castration resistant prostate cancer.