5002 Background: There is no standard of care when pts with metastatic HRPC manifest disease progression (PD) after 1st-line docetaxel. Custirsen is an antisense oligonucleotide targeting clusterin which in preclinical studies increased response of taxane-resistant cell lines to chemotherapy. This study evaluated the safety and efficacy of custirsen in combination with either docetaxel or mitoxantrone as 2nd-line therapy (Rx). Methods: Pts were eligible if they had PD while receiving or within 6 mo of discontinuing 1st-line docetaxel. All pts received 640 mg of weekly IV custirsen following 3 loading doses. Pts were randomized to standard doses of docetaxel/prednisone (DPC) or mitoxantrone/prednisone (MPC) on a 21-day cycle for up to 9 cycles. Protocol defined PD was based on RECIST, pain and performance score but not solely on PSA. Results: Analysis as of 03Jan08; median follow-up:13.3 (8.4- 17.1) mo. 42 pts received at least 1 cycle of combined therapy (DPC-20, MPC-22). Prior outcomes with 1st-line doce...