期刊
CLINICAL CANCER RESEARCH
卷 19, 期 18, 页码 5182-5191出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-0231
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资金
- Prostate Cancer Foundation
- National Institutes of Health [ULI RR024996, 1-KL2-RR024997-01, K23 CA102544-05, PTBF5405]
- Department of Defense [W81XWH-04-1-0267]
- David H. Koch Foundation
- Peter M. Sacerdote Foundation
- Robert Dow Foundation
- Robert H. McCooey Memorial Cancer Research Fund
Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; Lu-177) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. Experimental Design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of Lu-177-J591 (15 patients at 65 mCi/m(2), 17 at 70 mCi/m(2)) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m(2) to verify response rate and examine biomarkers. Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received Lu-177-J591. A total of 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. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m(2)) 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 nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. Conclusion: A single dose of Lu-177-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. (C) 2013 AACR.
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