Phase I/Ii Double-Blinded Randomized Study To Determine The Tolerability And Efficacy Of Two Different Doses Of Lenalidomide (Len) In Biochemically Relapsed Prostate Cancer (Brpc) (M0) Patients (Pts).

4554 Background: Preliminary data suggest that Len, an immunomodulatory agent and angiogenesis inhibitor, is active in prostate cancer. Aims: Evaluate the safety and efficacy of 6 months (mo) administration of 5 or 25 mg/day of Len. Methods: 60 noncastrate BRPC pts were stratified (PSADT, surgery/RT, prior ADT, Gleason) and randomized to oral Len at 5 (n=26) or 25 mg/day (n=34) given 3/4 weeks for 6 mo or until PSA progression (> 25% over baseline), clinical/radiographic progression or dose-limiting toxicity (tox). Disease status was evaluated at the end of every 6 mo cycle with scans and PSAs (collected/2 mo, assayed at 6 mo) and tox monthly. The proportion of pts with disease progression or dose limiting tox at 6 mo was compared between arms by chi-square test. Regression of the log PSA on the time of PSA measurement for each pt before and on study, was used to calculate pre and on study PSA slopes. The change in slope, on study slope minus pre study slope, was estimated for each pt and the mean changes for the two dose groups compared using a t-test. Results: Pre study parameters were balanced between arms. The occurrence of grade 3/4 tox was 11.5% with 5 mg and 29.4% with 25 mg, p=0.1, most commonly neutropenia (5 pts, all on 25 mg), venous thromboembolism (2 in each group), fatigue (2), skin rash (2). Mean (range) steady state Len plasma concentration (ng/ml) was 12.67 (6.1-19.2) versus 65.14 (24.3-106.0), p=0.01, for 5mg and 25mg respectively. Mean (range) follow up (mo) is 28.3±10.4 (12-41). A significant decrease in PSA slope favored the 25 mg (-0.172 vs. -0.033, p = 0.005) (Table). 50% and 44% of pts on 5 mg and 25 mg respectively, had PSA/scans progression at 6 mo. Currently 9 patients are still on study, 6 on 25 mg and 3 on 5 mg. Conclusions: Long-term Len treatment has acceptable tox, results in dose-dependent changes in PSA slope, and potentially delays progression of BRPC (M0). Randomized studies evaluating conventional disease endpoints should be performed. 5 mg 25 mg p value Mean (95% CI) pre-study PSA slope 0.16 (0.11 to 0.21) 0.18 (0.13 to 0.23) 0.55 Mean (95% CI) pre/post PSA slope −0.033 (−0.11 to 0.04) −0.172 (−0.24 to −0.11) 0.005 No significant financial relationships to disclose.