OBJECTIVES: . A docetaxel (D)-based regimen is recommended first-line treatment for mHRPC patients. Currently, there are no recommended second-line treatments for D pre-treated patients. This study sought to identify phase II and III RCTs of second-line treatments for mHRPC in D pre-treated patients to provide information regarding survival. METHODS: . PubMed and Embase were used to perform a systematic literature review (2000-2009). Primary and secondary efficacy endpoints were extracted. Safety outcomes were reviewed according to grade. RESULTS: Among 52 records screened, 3 trials were included and 47 were excluded (35 not clinical trials; 4 not second line to D; 8 not comparative or randomised). Primary endpoints included Overall-Survival (OS), Progression-Free-Survival(PFS), PSA response rate and Objective-Tumor-Response (OTR) . A phase III study comparing satraplatin plus prednisone (SP) to prednisone (P) alone (n=950, 51% post-D) was identified. Two phase II trials compared ixabepilone (ixa) with mitoxantrone plus prednisone (MP) (n=82), and custirsen in combination with prednisone plus D (DPC) versus curtisen plus MP (MPC) (n=42). SP demonstrated  significant improvements compared to P in PSA response (25% vs. 12%, p<0.001), OTR (7% vs. 1%, p<0.002) and pain response (24% vs. 14%, p<0.005). Median PFS (11 wks vs. 9.7 wks) but median OS (66.1 wks vs. 62.9 wks) were similar. In the second trial (Ixa vs. MP) there was no significant improvement in either PSA response (17% vs 20%) or OS. In the third trial, PSA response was better for DPC than MPC (40% vs 27%); no OS data reported. Grade 3 or 4 neutropenia occurred in 54% and 63% with Ixa and MP respectively.  CONCLUSIONS: . This review found a limited number of published phase II and III RCTs second-line treatments for mHRPC in D pre-treated patients. None demonstrated a survival benefit. Results should be interpreted with caution in terms of clinical benefits