153 ISSN 1479-6694 10.2217/FON.13.243 © 2014 Future Medicine Ltd Future Oncol. (2014) 10(2), 153–155 An unprecedented large number of agents capable of prolonging survival is presently available for patients with castrationresistant prostate cancer (CRPC) [1,2]. Survival expectancy of a patient with newly diagnosed CRPC has approximately doubled since the approval of docetaxel, although it still appears to be poor in selected populations [3,4], such as those with primary refractoriness to docetaxel [5]. US FDAand EMA-approved agents now include immunotherapy agent sipuleucel-T, CYP17A inhibitor abiraterone, antiandrogen receptor enzalutamide, cytotoxic agent cabazitaxel and radiopharmeceutical agent radium-223. These agents were approved in different settings. While sipuleucel-T was mainly tested in minimally symptomatic, chemotherapy-naive patients, abiraterone, enzalutamide and cabazitaxel were tested in patients pretreated with docetaxel. Radium-223 was approved in patients who were either ineligible to or refused or had already received docetaxel, and had symptomatic diffuse bone metastases. Although abiraterone proved to prolong progression-free survival in chemotherapy-naive patients, with a statistically significant improvement in overall survival that did not satisfy the statistical boundaries required by the study design, the potential detrimental effect on survival that postponing docetaxel in a population of metastatic CRPC might have was not adequately accounted for in this trial, and an opportunity to test sequential therapies was missed [6]. With multiple available effective agents, their optimal sequential use, their use in selected populations and the early assessment of efficacy in individual patients are three main issues. A few recently published case series showed only modest efficacy of cabazitaxel, abiraterone and enzalutamide when used as third-line agents, although prospective data are lacking. In 24 patients treated with cabazitaxel after docetaxel and abiraterone, a median of four cycles of cabazitaxel were delivered, with a median survival from initiation of cabazitaxel of 8.2 months (95% CI: 3.34–13.05) [7], and a median survival after docetaxel initiation of 32 months. In 35 patients treated with the sequence enzalutamide after docetaxel and abiraterone, a greater than 50% PSA decline was recorded in 45.7% of patients,