Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)

Abstract

Abiraterone and prednisolone have modest antitumour activities in patients with mCRPC pretreated with docetaxel and enzalutamide.

Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer

“…Cells were fixed with formaldehyde (3.7%), permeabilized using PBS (0.1% TRITON X-100), and incubated overnight possible mechanistic advantage of CYP17 inhibitors compared with that of pure antiandrogens (15). Studies have suggested that there is considerable cross-resistance to abiraterone in patients progressing on enzalutamide treatment, although a few patients did show decreases in their PSA levels (55,56). It will be informative in future studies to address whether these responders were due to abiraterone-inhibitory activity on AR mutants, such as F876L.…”

Treatment of metastatic prostate cancer

“…15 Small gains in a minority of patients were demonstrated when abiraterone was given following enzalutamide, albeit in two small cohorts where 25-29% of patients were Eastern Cooperative Oncology Group performance status 2. 16,17 In a series of 35 patients receiving enzalutamide following abiraterone and docetaxel, the median time to progression was just 4 months. 18 Results of ongoing trials are awaited; however, it is clear that predictive biomarkers are urgently needed to inform treatment sequencing, and understanding the mechanisms of resistance is key.…”

Avances en el tratamiento de cáncer de próstata resistente a la castración: énfasis en nuevas terapias hormonales

“…Reportes iniciales parecen coincidir que las respuestas a AA post enzalutamida (o viceversa) son menores que al tratamiento primario [60][61][62][63] . Agregando mayor complejidad a la elección de tratamiento inicial, estudios preclínicos sugieren cierta superposición en los mecanismos de acción y por lo tanto, resistencia cruzada parcial entre taxanos y hormonoterapia [64][65] , fenómeno que sería menor en el caso de cabazitaxel 66 .…”