Background: Although EP exerts a synergism with D and a meta-analysis suggested a survival advantage in combining EP to chemotherapy, D+EP combination is usually discouraged due to a marginal improvement in disease control at cost of an enhanced toxicity compared to D alone. In order to assess the role of EP added to D we have analyzed data from pts enrolled in two randomized trials with D ± EP conducted by our group (BJU Int 2008 – ASCO GU 2012). Methods: All patients received D 70 mg/m²IV q 3 wks ± E 280 mg/TID PO for 5 days starting 1 day prior to D. Ninety-five pts of the first study (started in 2002) were treated until progression; 148 pts of the second study received 8 D courses in continuous or intermittent fashion. We evaluated PSA response, PFS according to PCWG2, OS and toxicity. Results: We shared the clinical data from all 243 pts (123 D, 120 D+EP): the median baseline PSA values were 53 and 60 respectively; 49.5% and 59.1% of the D and D+EP pts presented visceral metastases, respectively. Clinical outcomes and main toxicities are summarized in the Table. Conclusions: The addition of EP to D was tolerable with a mild toxicity profile; it was able to double the biochemical responses which did not translate in any PFS or OS advantage. From our data the addition of EP addition to D should not further role in first line of CRPC, while it may help to overcome D resistance in selected cases according to our previously published data (Urol Oncol 2010). However, this statement should be critically considered at the light of new drugs availabile and active after D failure. Clinical trial information: 2006-005728-17.