121 Background: A phase II trial in men with progressive metCRPC receiving a single dose of 177Lu-J591 at 65 mCi/m2 (15 pts) or 70 mCi/m2 (phase I MTD, 17 pts) was performed without selection for PSMA expression, suggesting a larger than expected dose-response (13 vs 47% >30% PSA decline respectively), leading to an expansion cohort to validate the response rate at 70 mCi/m2. Methods: Endpoints: to validate the PSA and/or measurable disease response at 70 mCi/m2, evaluate circulating tumor cell counts (CellSearch) and pre-treatment PSMA imaging with 111In-J591 in the expansion cohort, and examine overall survival (OS) for all pts. Results: 15 additional pts were treated. Expansion cohort demographics were similar to the initial cohorts, and PSA responses and toxicity were similar to the initial cohort treated at 70 mCi/m2 (see Table), with myelotoxicity improving in all following nadir at 1 month. More PSA declines and longer OS were seen at 70 mCi/m2. 12 of 15 pts had baseline and follow up CTC counts at 4-6 weeks: 66.7% had >50% decline and 25% were unchanged at 0 or 1 (one declined 27%). Although 93.3% had accurate targeting (imaging) of known sites of disease, as seen in initial analysis, a trend for fewer > 30% PSA declines was seen with less intense PSMA imaging. Conclusions: Single dose 177Lu-J591 at70 mCi/m2 was generally well tolerated, with predictable, reversible myelosuppression, and demonstrates anti-tumor activity in pts with progressive metCRPC. A dose-response relationship was confirmed for both toxicity and activity, with improved response and OS at 70 mCi/m2. CTC declines are demonstrated. Selection of pts based upon non-invasive testing (PSMA imaging) may improve the therapeutic profile. Clinical trial information: NCT00195039. [Table: see text]
4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice