Randomized phase III trial of thalidomide (Th) or placebo (P) for non-metastatic PSA recurrent prostate cancer (PCa) treated with intermittent therapy.

5016 Background: Th has modest activity in pts with metastatic PCa (CCR 2001; 7:1888 and JCO 2004; 22:2532). LHRH agonist (LHRH-A) therapy is used in PCa pts with PSA recurrence. This trial was undertaken to determine if Th improves progression-free survival (PFS) after limited androgen deprivation therapy in pts with biochemical recurrence.,This was a randomized, double-blind, placebo-controlled, cross-over study in pts with biochemical recurrence after local definitive therapy. Pts were randomized to oral Th or P in blinded fashion following 24 weeks of LHRH-A [designated oral phase A (OPA)]. Baseline and monthly PSA and testosterone (T) were obtained while on Th or P, until rise to baseline PSA or rise of PSA to ≥ 5 ng/mL, whichever occurred first. LHRH-A was then re-initiated after a second 24 weeks of LHRH-A, oral treatment then commenced with the opposite agent (Th to P or P to Th), until PSA progression, designated as [oral phase B (OPB)]. Secondary endpoints included characterization of pharmacokinetics, toxicity and drug effect on T.,159 pts accrued from March 2000 to January 2005; 79 randomized to Th and 80 to P in OPA, of whom 73 and 74 respectively received study drug. Pt characteristics included a median (range) age of 68 (49-87), median Gleason score of 7, median (range) on-study PSA of 5.1 ng/mL (0.9 - 311.8). 46 and 62 pts progressed on Th and P, respectively during OPA. Median PFS during OPA was 15 months (mos) for Th arm compared to 9.6 mos for P arm (P=0.21). 103 pts proceeded to OPB, of whom 51 pts received Th and 38 pts received P. Median PFS during OPB for the Th arm was 17.1 mos versus 6.6 mos for the P arm (P=0.0002). Grade 3 or 4 events occurred in ≤5% of pts on Th. Most common grade 2 toxicites: constipation, fatigue, neurologic (e.g., dizziness, change in consciousness, neuropathy), and dyspnea. T normalization was similar in Th and P arms.,Th was associated with improvement in PSA-based PFS after intermittent LHRH-A that was independent of effects on T. Th appears promising in this clinical state. Larger studies are warranted to determine the clinical utility of this approach. No significant financial relationships to disclose.