Randomized phase II trial of irofulven (IROF)/prednisone (P), IROF/capecitabine (C)/P or mitoxantrone (M)/P in docetaxel-pretreated hormone refractory prostate cancer (HRPC) patients (pts)

14513 Background: IROF, a semisynthetic derivative of the natural product illudin S, is a novel DNA binding agent. IROF alone or in combination has shown activity in phase I-II trials in HRPC, notably with IROF/C (Cvitkovic et al, ASCO 2004). Methods: Pts with histologically-proven metastatic HRPC who progressed (RECIST or PSA) during prior docetaxel or within 3 months of discontinuing treatment, with adequate hematologic and organ functions and KPS ≥70% were stratified by pain and randomized to one of three treatments: Arm A: IROF (0.45 mg/kg, day 1 and 8 q3weeks [w]) and P (10 mg po daily); Arm B: IROF (0.4 mg/kg day 1 and 15), C(2000 mg/m2 day 1–15 q4w) and P; or Arm C: M (12 mg/m2 q3w) and P. Primary endpoint was TTP (RECIST, PSA or clinical progression); secondary endpoints included PSA response (≥50% decrease for ≥4 w), pain response, and toxicity; 135 pts are planned in a 2:2:1 ratio. The study was powered to detect a difference in TTP of 1.5 vs 3 months. Results: As of Dec 2005, 78 pts were random...