PURPOSE: To assess the efficacy of a single infusion of radiolabeled anti-prostate specific membrane antigen monoclonal antibody J591 (177Lu-J591) by PSA decline, measurable disease response, and survival.
EXPERIMENTAL DESIGN: In this dual-center phase II study, 2 cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177Lu-J591 (15 patients at 65 mCi/m2, 17 at 70 mCi/m2) with radionuclide imaging. Expansion cohort (n=15) received 70 mCi/m2 to verify response rate and examine biomarkers.
RESULTS: 47 patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177Lu-J591. 10.6% experienced > 50% decline in PSA, 36.2% experienced > 30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. 25.5% experienced grade 4 neutropenia with 1 episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m2) resulted in more 30% PSA declines (46.9% vs 13.3%, p=0.048) and longer survival (21.8 vs 11.9 months, p=0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious non-hematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond.
CONCLUSIONS: A single dose of 177Lu-J591 was well-tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose-response. Imaging biomarkers appear promising.
Written by:
Tagawa ST, Milowsky MI, Morris MJ, Vallabhajosula S, Christos PJ, Akhtar NH, Goldsmith SJ, Osborne J, Larson SM, Pandit-Taskar N, Scher HI, Bander NH, Nanus DM. Are you the author?
Medicine:Hematology/Oncology and Urology, Weill Cornell Medical College.
Reference: Clin Cancer Res. 2013 May 28. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-13-0231
PubMed Abstract
PMID: 23714732
