Castration-resistant prostate cancer: current status of therapy with Radium-223 associated with anti-androgens (enzalutamide and abiraterone) - a systematic literature review

Resumo

BACKGROUND. Recently, a new range of therapeutic options became available for men with advanced castration-resistant prostate cancer (CRPC), including antiandrogens (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and a radionuclide (radium-223). The development of abiraterone and enzalutamide, as well as the advent of Ra-223, led to significant improvements in CRPC clinical outcomes. However, there are currently few data regarding the optimal sequence or concomitant use of Ra-223 with these most recently approved endocrine agents. OBJECTIVE. To systematically identify and analyse articles that brings information about the concomitant or sequential use of radium-223 (Ra-223) associated with antiandrogenic drugs (abiraterone or enzalutamide) in the therapy of CRPC. METHODS. PubMed (mesh and free terms), Scopus and Clinical Trials were searched to identify published articles about the sequential or association use of radium-223. RESULTS. A total of 484 references were identified by the literature search and after exclusion and inclusion criteria 36 were screened. 4 publications that met the selection criteria were included in this review; of these 2 were cost-effectiveness studies and 2, case series. Overall, safety profiles in relation to therapy with Ra-223 were similar regardless of use or not of enzalutamide or abiraterone. Response were higher for the combinations of Ra-223 with abiraterone while with enzalutamide no improvements were found. The drugs do not seem to have great differences in costs and there is still no consensus on the most cost-effective treatment in the short and long term. CONCLUSION. Further studies are necessary to evaluate the best treatment regimen (concurrent or sequential) of Ra-223 and new antiandrogens. By now, data show that the best association of use may be with abiraterone. There are ongoing clinical trials that aim to precisely study the use of these drugs together, therefore in the next few years this situation tends to change.